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1.
Arq. bras. med. vet. zootec. (Online) ; 72(5): 1797-1804, Sept.-Oct. 2020. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1131531

ABSTRACT

The aim of this study was to evaluate the reproductive traits of the non-inbred and inbred AquaAmérica, GIFT and AquaAmérica × GIFTgenetic groups. Six fish from each genetic group were used (2 females:1 male). Females were examined for the presence of eggs in their mouth at every four days, for 12 weeks. Reproduction occurred in all genetic groups (GIFT: 100%; non-inbred AquaAmérica and AquaAmérica ×GIFT: 75%; inbred AquaAmérica: 50%). Female weight, female standard length, total spawning weight, absolute fecundity, relative fecundity, spawn index and hatching rate did not differ significantly between the genetic groups. However, the non-inbred AquaAmérica variety showed lower values (P<0.05) for egg diameter (2.4mm) and egg weight (4.2mg) and higher values (P<0.05) for relative number of eggs (247.6 eggs/g of egg) than GIFT (egg diameter: 2.8mm; egg weight: 5.7mg; relative number of eggs: 175.4 eggs/g of egg) and AquaAmérica ×GIFT (egg diameter: 2.8mm; egg weight: 5.9mg; relative number of eggs: 168.8 eggs/g of egg). In conclusion, the non-inbred AquaAmérica variety produces smaller, lighter eggs but a higher relative number of eggs than the GIFT variety and the AquaAmérica ×GIFT cross; and inbreeding negatively affects spawning rate.(AU)


O objetivo deste estudo foi avaliar as características reprodutivas dos grupos genéticos AquaAmérica não endogâmicos e endogâmicos, GIFT e AquaAmérica × GIFT. Foram utilizados seis peixes de cada grupo genético (duas fêmeas:um macho). As fêmeas foram examinadas quanto à presença de ovos na boca a cada quatro dias, durante 12 semanas. A reprodução ocorreu em todos os grupos genéticos (GIFT: 100%; AquaAmérica não endogâmica e AquaAmérica × GIFT: 75%; AquaAmérica endogâmica: 50%). Peso e comprimento padrão de fêmea, peso total de desova, fecundidade absoluta, fecundidade relativa, índice de desova e taxa de eclosão não diferiram significativamente entre os grupos genéticos. Entretanto, a variedade não endogâmica da AquaAmérica apresentou valores mais baixos (P<0,05) para diâmetro do ovo (2,4mm) e peso do ovo (4,2mg) e maiores valores (P<0,05) para número relativo de ovos (247,6 ovos/g de ovo ) que GIFT (diâmetro do ovo: 2,8mm; peso do ovo: 5,7mg; número relativo de ovos: 175,4 ovos/g de ovo) e AquaAmérica × GIFT (diâmetro do ovo: 2,8mm; peso do ovo: 5,9mg; número relativo de ovos: 168,8 ovos/g de ovo). Em conclusão, a variedade AquaAmérica não endogâmica produz ovos menores e mais leves, mas um número relativo maior de ovos que a variedade GIFT e o cruzamento AquaAmérica × GIFT; a consanguinidade afeta negativamente a taxa de desova.(AU)


Subject(s)
Animals , Reproduction/physiology , Cichlids/genetics , Genetic Enhancement/methods , Animals, Inbred Strains/genetics , Animals, Outbred Strains/genetics
2.
PLoS Genet ; 15(11): e1008446, 2019 11.
Article in English | MEDLINE | ID: mdl-31725724

ABSTRACT

For over a century, mice have been used to model human disease, leading to many fundamental discoveries about mammalian biology and the development of new therapies. Mouse genetics research has been further catalysed by a plethora of genomic resources developed in the last 20 years, including the genome sequence of C57BL/6J and more recently the first draft reference genomes for 16 additional laboratory strains. Collectively, the comparison of these genomes highlights the extreme diversity that exists at loci associated with the immune system, pathogen response, and key sensory functions, which form the foundation for dissecting phenotypic traits in vivo. We review the current status of the mouse genome across the diversity of the mouse lineage and discuss the value of mice to understanding human disease.


Subject(s)
Animals, Inbred Strains/genetics , Genome/genetics , Genomics , Animals , Chromosome Mapping , Haplotypes , Humans , Inbreeding , Mice , Phenotype
3.
Exp Anim ; 67(1): 83-90, 2018 Feb 09.
Article in English | MEDLINE | ID: mdl-29046492

ABSTRACT

The Mongolian gerbil has been a useful laboratory animal in many research fields, especially in ischemia studies. However, due to the variation of the circle of Willis (COW), the ischemic model is unstable and various. To solve this problem, we newly established an inbred strain of gerbils, restricting breeding and keeping to F23. The data on the breeding and growth of the animals are described in the present study. The genetic characteristics of F4 to F20 detected by microsatellite DNA and biochemical markers are also shown here. The results demonstrated that the frequency of ischemic model by unilateral carotid occlusion and the frequency of incomplete COW increased, increasing from 50% and 75% in F1 to 88.89% and 100% in F20, respectively. The ratios of consistent patterns of COW in parents were positively related with the number of inbred generations. A reproductive performance analysis indicated that the average size of litters in the inbred gerbils was less than that of outbred gerbils and that adult body weight was also lower in inbred gerbils; also, the pups in the 2nd litter were the best ones chosen to reproduce. The genetic detection results indicated that 26 out of 28 microsatellite loci and all 26 biochemical markers were homozygous in F20, showing comparably identical genetic composition in inbred gerbils. All the data demonstrated that an inbred strain of ischemia-prone gerbil has been established successfully. This strain can be used in stroke research and can largely reduce the number of animals needed in experiments.


Subject(s)
Animals, Inbred Strains/genetics , Animals, Inbred Strains/physiology , Brain Ischemia , Breeding/methods , Disease Models, Animal , Gerbillinae/genetics , Gerbillinae/physiology , Reproduction , Anatomic Variation , Animals , Body Weight , Circle of Willis/anatomy & histology , DNA/genetics , Litter Size , Microsatellite Repeats/genetics
4.
Biogerontology ; 17(5-6): 883-892, 2016 11.
Article in English | MEDLINE | ID: mdl-27488377

ABSTRACT

An extremely high (about 100 %) increase in longevity is reported for a subset of recombinant inbred lines (RILs) of Drosophila melanogaster subjected to a cyclic heat stress throughout the adult life. Previous work showed that both longevity and heat sensitivity highly differed among RILs. The novel heat stress treatment used in this study consisted of 5 min at 38 °C applicated approximately every 125 min throughout the adult life starting at the age of 2 days. In spite of the exceptionally high increase in longevity in a set of RILs, the same heat stress treatment reduced rather than increased longevity in other RILs, suggesting that heat-induced hormesis is dependent on the genotype and/or the genetic background. Further, one quantitative trait locus (QTL) was identified for heat-induced hormesis on chromosome 2 (bands 28A1-34D2) in one RIL panel (RIL-D48) but it was not significant in its reciprocal panel (RIL-SH2). The level of heat-induced hormesis showed a sexual dimorphism, with a higher number of lines exhibiting higher hormesis effects in males than in females. The new heat stress treatment in this study suggests that longevity can be further extended than previously suggested by applying a cyclic and mild stress throughout the life, depending on the genotype.


Subject(s)
Aging/genetics , Drosophila melanogaster/genetics , Heat-Shock Response/genetics , Longevity/genetics , Animals , Animals, Inbred Strains/genetics , Drosophila Proteins/genetics , Female , Gene Expression Regulation, Developmental/genetics , Hormesis/genetics , Male , Quantitative Trait Loci/genetics , Recombination, Genetic/genetics , Sex Characteristics , Thermotolerance/genetics
5.
Alcohol Clin Exp Res ; 39(4): 611-20, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25833023

ABSTRACT

BACKGROUND: We previously reported that acute functional tolerance (AFT) to the hypnotic effects of alcohol was significantly correlated with drinking in the dark (DID) in the LXS recombinant inbred panel, but only in mice that had been pretreated with alcohol. Here, we have conducted quantitative trait locus (QTL) mapping for AFT. DNA sequencing of the progenitor ILS and ISS strains and microarray analyses were also conducted to identify candidate genes and functional correlates. METHODS: LXS mice were given either saline or alcohol (5 g/kg) on day 1 and then tested for loss of righting reflex AFT on day 2. QTLs were mapped using standard procedures. Two microarray analyses from brain were conducted: (i) naïve LXS mice and (ii) an alcohol treatment time course in the ILS and ISS. The full genomes of the ILS and ISS were sequenced to a depth of approximately 30×. RESULTS: A significant QTL for AFT in the alcohol pretreatment group was mapped to distal chromosome 4; numerous suggestive QTLs were also mapped. Preference drinking and DID have previously been mapped to the chromosome 4 locus. The credible interval of the significant chromosome 4 QTL spanned 23 Mb and included 716 annotated genes of which 150 had at least 1 nonsynonymous single nucleotide polymorphism or small indel that differed between the ILS and ISS; expression of 48 of the genes was cis-regulated. Enrichment analysis indicated broad functional categories underlying AFT, including proteolysis, transcription regulation, chromatin modification, protein kinase activity, and apoptosis. CONCLUSIONS: The chromosome 4 QTL is a key region containing possibly pleiotropic genes for AFT and drinking behavior. Given that the region contains many viable candidates and a large number of the genes in the interval fall into 1 or more of the enriched functional categories, we postulate that many genes of varying effect size contribute to the observed QTL effect.


Subject(s)
Alcohol Drinking/genetics , Drug Tolerance/genetics , Ethanol/pharmacology , Quantitative Trait Loci/genetics , Reflex, Righting/drug effects , Animals , Animals, Inbred Strains/genetics , Brain/drug effects , Chromosome Mapping , Gene Expression Profiling , Genetic Association Studies , Genotype , Male , Mice
6.
Mol Biol Evol ; 32(1): 81-90, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25234703

ABSTRACT

Because self-incompatibility loci are maintained heterozygous and recombination within self-incompatibility loci would be disadvantageous, self-incompatibility loci are thought to contribute to structural and functional differentiation of chromosomes. Although the hermaphrodite chordate, Ciona intestinalis, has two self-incompatibility genes, this incompatibility system is incomplete and self-fertilization occurs under laboratory conditions. Here, we established an inbred strain of C. intestinalis by repeated self-fertilization. Decoding genome sequences of sibling animals of this strain identified a 2.4-Mbheterozygous region on chromosome 7. A self-incompatibility gene, Themis-B, was encoded within this region. This observation implied that this self-incompatibility locus and the linkage disequilibrium of its flanking region contribute to the formation of the 2.4-Mb heterozygous region, probably through recombination suppression. We showed that different individuals in natural populations had different numbers and different combinations of Themis-B variants, and that the rate of self-fertilization varied among these animals. Our result explains why self-fertilization occurs under laboratory conditions. It also supports the concept that the Themis-B locus is preferentially retained heterozygous in the inbred line and contributes to the formation of the 2.4-Mb heterozygous region. High structural variations might suppress recombination, and this long heterozygous region might represent a preliminary stage of structural differentiation of chromosomes.


Subject(s)
Animals, Inbred Strains/genetics , Ciona intestinalis/genetics , Heterozygote , Animals , Animals, Inbred Strains/physiology , Chromosomes , Ciona intestinalis/physiology , Genetic Loci , Genetic Variation , Self-Fertilization , Sequence Analysis, DNA
7.
BMC Genomics ; 14: 148, 2013 Mar 05.
Article in English | MEDLINE | ID: mdl-23497037

ABSTRACT

BACKGROUND: In contrast to international pig breeds, the Iberian breed has not been admixed with Asian germplasm. This makes it an important model to study both domestication and relevance of Asian genes in the pig. Besides, Iberian pigs exhibit high meat quality as well as appetite and propensity to obesity. Here we provide a genome wide analysis of nucleotide and structural diversity in a reduced representation library from a pool (n=9 sows) and shotgun genomic sequence from a single sow of the highly inbred Guadyerbas strain. In the pool, we applied newly developed tools to account for the peculiarities of these data. RESULTS: A total of 254,106 SNPs in the pool (79.6 Mb covered) and 643,783 in the Guadyerbas sow (1.47 Gb covered) were called. The nucleotide diversity (1.31x10-3 per bp in autosomes) is very similar to that reported in wild boar. A much lower than expected diversity in the X chromosome was confirmed (1.79x10-4 per bp in the individual and 5.83x10-4 per bp in the pool). A strong (0.70) correlation between recombination and variability was observed, but not with gene density or GC content. Multicopy regions affected about 4% of annotated pig genes in their entirety, and 2% of the genes partially. Genes within the lowest variability windows comprised interferon genes and, in chromosome X, genes involved in behavior like HTR2C or MCEP2. A modified Hudson-Kreitman-Aguadé test for pools also indicated an accelerated evolution in genes involved in behavior, as well as in spermatogenesis and in lipid metabolism. CONCLUSIONS: This work illustrates the strength of current sequencing technologies to picture a comprehensive landscape of variability in livestock species, and to pinpoint regions containing genes potentially under selection. Among those genes, we report genes involved in behavior, including feeding behavior, and lipid metabolism. The pig X chromosome is an outlier in terms of nucleotide diversity, which suggests selective constraints. Our data further confirm the importance of structural variation in the species, including Iberian pigs, and allowed us to identify new paralogs for known gene families.


Subject(s)
Animals, Inbred Strains/genetics , Chromosome Mapping , Polymorphism, Single Nucleotide/genetics , Swine/genetics , Animals , Breeding , Genetic Variation , Nucleotides/genetics
8.
Article in English | MEDLINE | ID: mdl-23047051

ABSTRACT

Although the zebrafish (Danio rerio) has been widely utilized as a model organism for several decades, there is little information available on physiological variation underlying genetic variation among the most commonly used inbred strains. This study evaluated growth performance using physiological and molecular markers of growth in response to fasting in six commonly used zebrafish strains [AB, TU, TL, SJA, WIK, and petstore (PET) zebrafish]. Fasting resulted in a standard decrease in whole blood glucose levels, a typical vertebrate glucose metabolism pattern, in AB, PET, TL, and TU zebrafish strains. Alternatively, fasting did not affect glucose levels in SJA and WIK zebrafish strains. Similarly, fasting had no effect on myostatin mRNA levels in AB, PET, TU, and WIK zebrafish strains, but decreased myostatin-1 and -2 mRNA levels in SJA zebrafish. Consistent with previous work, fasting increased myostatin-2 mRNA levels in TL zebrafish. These data demonstrate that variation is present in growth performance between commonly used inbred strains of zebrafish. These data can help future research endeavors by highlighting the attributes of each strain with regard to growth performance so that the most fitting strain may be utilized.


Subject(s)
Food Deprivation , Gene Expression Regulation, Developmental , Myostatin/metabolism , Zebrafish Proteins/metabolism , Zebrafish/growth & development , Animals , Animals, Inbred Strains/genetics , Animals, Inbred Strains/growth & development , Animals, Inbred Strains/metabolism , Biomarkers/metabolism , Blood Glucose , Body Weight , Female , Genetic Variation , Glucose/analysis , Glucose/metabolism , Male , Muscles/cytology , Muscles/metabolism , Myostatin/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Species Specificity , Spleen/cytology , Spleen/metabolism , Time Factors , Zebrafish/genetics , Zebrafish/metabolism , Zebrafish Proteins/genetics
9.
Adv Gerontol ; 26(4): 594-600, 2013.
Article in Russian | MEDLINE | ID: mdl-24738245

ABSTRACT

Assortative mating and hypervariability as the result of genomic stress, caused by selection, appear the main components of the mechanism of intrapopulation polymorphism maintenance. Activation of genome transposable elements has contributed significantly to increasing of variability provoked by inbreeding. Copy number of transposone Hermes DNA evaluation in somatic tissues of Musca domestica individuals from the strains differ by the life span at all developmental stages used as the criterion of genome stability. Investigations funded by RFBR 12-04-01450-a and 11-04-97005-r_povolzhje_a.


Subject(s)
DNA Transposable Elements/genetics , Genes, Insect , Houseflies/genetics , Longevity/genetics , Polymorphism, Genetic , Animals , Animals, Inbred Strains/genetics , Genetic Vectors , Genomic Instability/genetics , Inbreeding , Molecular Sequence Data , Repetitive Sequences, Nucleic Acid
10.
Mol Ecol Resour ; 12(6): 975-82, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23227485

ABSTRACT

In spite of the usefulness of codominant markers in population genetics, the existence of null alleles raises challenging estimation issues in natural populations that are characterized by positive inbreeding coefficients (F > 0). Disregarding the possibility of F > 0 in a population will generally lead to overestimates of null allele frequencies. Conversely, estimates of inbreeding coefficients (F) may be strongly biased upwards (excess homozygotes), in the presence of nontrivial frequencies of null alleles. An algorithm has been presented for the estimation of null allele frequencies in inbred populations (van Oosterhout method), using external estimates of the F-statistics. The goal of this study is to introduce a modification of this method and to provide a formal comparison with an alternative likelihood-based method (Chybicki-Burczyk). Using simulated data, we illustrate the strengths and limitations of these competing methods. Under most circumstances, the likelihood method is preferable, but for highly inbred organisms, a modified van Oosterhout method offers some advantages.


Subject(s)
Animals, Inbred Strains/genetics , Biostatistics/methods , Gene Frequency , Algorithms , Animals , Computer Simulation
11.
Genet Sel Evol ; 44: 39, 2012 Dec 07.
Article in English | MEDLINE | ID: mdl-23216664

ABSTRACT

BACKGROUND: Using a multi-breed reference population might be a way of increasing the accuracy of genomic breeding values in small breeds. Models involving mixed-breed data do not take into account the fact that marker effects may differ among breeds. This study was aimed at investigating the impact on accuracy of increasing the number of genotyped candidates in the training set by using a multi-breed reference population, in contrast to single-breed genomic evaluations. METHODS: Three traits (milk production, fat content and female fertility) were analyzed by genomic mixed linear models and Bayesian methodology. Three breeds of French dairy cattle were used: Holstein, Montbéliarde and Normande with 2976, 950 and 970 bulls in the training population, respectively and 964, 222 and 248 bulls in the validation population, respectively. All animals were genotyped with the Illumina Bovine SNP50 array. Accuracy of genomic breeding values was evaluated under three scenarios for the correlation of genomic breeding values between breeds (r(g)): uncorrelated (1), r(g) = 0; estimated r(g) (2); high, r(g) = 0.95 (3). Accuracy and bias of predictions obtained in the validation population with the multi-breed training set were assessed by the coefficient of determination (R(2)) and by the regression coefficient of daughter yield deviations of validation bulls on their predicted genomic breeding values, respectively. RESULTS: The genetic variation captured by the markers for each trait was similar to that estimated for routine pedigree-based genetic evaluation. Posterior means for rg ranged from -0.01 for fertility between Montbéliarde and Normande to 0.79 for milk yield between Montbéliarde and Holstein. Differences in R(2) between the three scenarios were notable only for fat content in the Montbéliarde breed: from 0.27 in scenario (1) to 0.33 in scenarios (2) and (3). Accuracies for fertility were lower than for other traits. CONCLUSIONS: Using a multi-breed reference population resulted in small or no increases in accuracy. Only the breed with a small data set and large genetic correlation with the breed with a large data set showed increased accuracy for the traits with moderate (milk) to high (fat content) heritability. No benefit was observed for fertility, a lowly heritable trait.


Subject(s)
Cattle/genetics , Genome , Quantitative Trait, Heritable , Animals , Animals, Inbred Strains/genetics , Bayes Theorem , Breeding , Dairying/methods , Fertility/genetics , Genetic Variation , Lactation/genetics , Models, Genetic , Models, Statistical , Pedigree
12.
Genet Sel Evol ; 44: 35, 2012 Nov 26.
Article in English | MEDLINE | ID: mdl-23181486

ABSTRACT

BACKGROUND: Genotype by environment interactions are currently ignored in national genetic evaluations of dairy cattle. However, this is often questioned, especially when environment or herd management is wide-ranging. The aim of this study was to assess genotype by environment interactions for production traits (milk, protein, fat yields and fat and protein contents) in French dairy cattle using an original approach to characterize the environments. METHODS: Genetic parameters of production traits were estimated for three breeds (Holstein, Normande and Montbéliarde) using multiple-trait and reaction norm models. Variables derived from Herd Test Day profiles obtained after a test day model evaluation were used to define herd environment. RESULTS: Multiple-trait and reaction norm models gave similar results. Genetic correlations were very close to unity for all traits, except between some extreme environments. However, a relatively wide range of heritabilities by trait and breed was found across environments. This was more the case for milk, protein and fat yields than for protein and fat contents. CONCLUSIONS: No real reranking of animals was observed across environments. However, a significant scale effect exists: the more intensive the herd management for milk yield, the larger the heritability.


Subject(s)
Cattle/genetics , Gene-Environment Interaction , Genotype , Models, Genetic , Models, Statistical , Quantitative Trait, Heritable , Animals , Animals, Inbred Strains/genetics , Dairying/methods , France
13.
Genet Sel Evol ; 44: 17, 2012 May 23.
Article in English | MEDLINE | ID: mdl-22620856

ABSTRACT

BACKGROUND: Cryopreservation of three endangered Belgian sheep breeds required to characterize their intra-breed genetic diversity. It is assumed that the genetic structure of a livestock breed depends mostly on gene flow due to exchanges between herds. To quantify this relation, molecular data and analyses of the exchanges were combined for three endangered Belgian breeds. METHODS: For each breed, between 91 and 225 sheep were genotyped with 19 microsatellites. Genetic differentiations between breeds and among herds within a breed were evaluated and the genetic structure of the breeds was described using Bayesian clustering (Structure). Exchanges of animals between 20, 46 and 95 herds according to breed were identified via semi-directed interviews and were analyzed using the concepts of the network theory to calculate average degrees and shortest path lengths between herds. Correlation between the Reynolds' genetic distances and the shortest path lengths between each pair of herds was assessed by a Mantel test approach. RESULTS: Genetic differentiation between breeds was high (0.16). Overall Fst values among herds were high in each breed (0.17, 0.11 and 0.10). Use of the Bayesian approach made it possible to identify genetic groups of herds within a breed. Significant correlations between the shortest path lengths and the Reynolds' genetic distances were found in each breed (0.87, 0.33 and 0.41), which demonstrate the influence of exchanges between herds on the genetic diversity. Correlation differences between breeds could be explained by differences in the average degree of the animal exchange networks, which is a measure of the number of exchanges per herd. The two breeds with the highest average degree showed the lowest correlation. Information from the exchange networks was used to assign individuals to the genetic groups when molecular information was incomplete or missing to identify donors for a cryobank. CONCLUSIONS: A fine-scale picture of the population genetic structure at the herd level was obtained for the three breeds. Network analysis made it possible to highlight the influence of exchanges on genetic structure and to complete or replace molecular information in establishing a conservation program.


Subject(s)
Animals, Inbred Strains/genetics , Genetic Variation , Sheep/genetics , Alleles , Animals , Gene Flow , Gene Regulatory Networks , Genetic Carrier Screening/methods , Genetic Loci , Genotype , Heterozygote , Microsatellite Repeats , Pedigree
14.
Mitochondrion ; 12(4): 438-40, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22609322

ABSTRACT

The Chillingham herd of wild Northumbrian cattle remains viable despite over 300 years of in-breeding and a near-homozygous nuclear genome. Here we report the complete mitochondrial DNA sequence using ultra-deep next generation sequencing. Random population sampling of ~10% of the extant herd identified a single mtDNA haplotype harbouring a unique bovine variant present in all other higher mammals (m.11789C/Y421H) which may contribute to their survival.


Subject(s)
Animals, Inbred Strains/genetics , DNA, Mitochondrial/genetics , Animals , Cattle , Cluster Analysis , Genome, Mitochondrial , Haplotypes , High-Throughput Nucleotide Sequencing , Phylogeny
15.
Autoimmunity ; 44(2): 159-65, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20670120

ABSTRACT

T helper type 17 (Th17) cells, a newly identified effector T-cell subset, have recently been shown to play a role in numerous autoimmune diseases, including iodine-induced autoimmune thyroiditis in non-obese diabetic (NOD)-H2(h4) mice, which had previously been thought Th1-dominant. We here studied the role of Th17 in Graves' hyperthyroidism, another thyroid-specific autoimmune disease, in a mouse model. Two genetically distinct BALB/c and NOD-H2(h4) strains with intact or disrupted IL-17 genes (IL-17(+/+) or IL-17(-/-)) were immunized with adenovirus (Ad) expressing the thyrotropin receptor (TSHR) A-subunit (Ad-TSHR289). Both IL-17(+/+) and IL-17(-/-) mice developed anti-TSHR antibodies and hyperthyroidism at equally high frequencies on the BALB/c genetic background. In contrast, some IL-17(+/+), but none of IL-17(-/-), mice became hyperthyroid on the NOD-H2(h4) genetic background, indicating the crucial role of IL-17 for development of Graves' hyperthyroidism in non-susceptible NOD-H2(h4), but not in susceptible BALB/c mice. In the T-cell recall assay, splenocytes and lymphocytes from the draining lymph nodes from either mouse strains, irrespective of IL-17 gene status, produced IFN-γ and IL-10 but not other cytokines including IL-17 in response to TSHR antigen. Thus, the functional significance of Th17 may not necessarily be predictable from cytokine expression patterns in splenocytes or inflammatory lesions. In conclusion, this is, to our knowledge, the first report showing that the role of Th17 cells for the pathogenesis of a certain autoimmune disease depends on the mouse genetic backgrounds.


Subject(s)
Animals, Inbred Strains/genetics , Graves Disease/genetics , Graves Disease/immunology , Receptors, Thyrotropin/metabolism , Th17 Cells/immunology , Animals , Autoimmune Diseases/genetics , Autoimmune Diseases/immunology , Autoimmune Diseases/physiopathology , Autoimmunity , Graves Disease/physiopathology , Mice/genetics , Mice, Inbred BALB C/genetics , Mice, Inbred NOD/genetics , Receptors, Thyrotropin/genetics , Thyrotropin/metabolism
16.
Toxicol Pathol ; 38(5): 681-90, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20562325

ABSTRACT

Methods of toxicity testing, barely changed for several decades, need to be improved. One way forward would be to use a small battery of inbred strains instead of the single outbred stock currently used in toxicity screening. Inbred strains are more stable, more uniform, more repeatable, and better defined than outbred stocks. Genetic variation would be observed as the difference between strains. Safety could be based on the most susceptible strain. Sometimes it may be possible to identify the genes involved. Mechanisms could be explored using gene expression profiling of susceptible and resistant strains. Two committees of toxicologists have concluded that the use of inbred strains, by controlling interindividual variability, would reduce the number of animals needed in toxicity screening, although both "preferred" outbred stocks. This preference appears to have been based on intuition rather than scientific principles. Data from a previously published study on the response to chloramphenicol in an outbred stock and four inbred strains is used to explain the advantages of the multistrain design. Toxicologists, safety pharmacologists, regulatory authorities, and pharmaceutical companies should take a critical look at the types of animals they use if they want to reduce the attrition rate of new drugs.


Subject(s)
Animals, Inbred Strains/genetics , Drug Evaluation, Preclinical/methods , Toxicity Tests/methods , Animals
17.
Obesity (Silver Spring) ; 16 Suppl 3: S28-32, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19037209

ABSTRACT

Obesity is known to be associated with variety of complex diseases including hypertension, cardiovascular disease, diabetes, affective disorders, and some cancers. The heterogeneous genetic (G) and environmental (E) conditions of human populations impart considerable difficulty for uncovering a common etiology between complex disease and their associated risk factors. Development of animal models where G and E variation are more controlled can provide a useful path for both mechanistic exploration and validation of human data. In 1996, we began development of what we thought would be more meaningful models for the study of complex disease. Based upon ideas on evolution of biologic complexity, we propose that aerobic capacity is mechanistically linked to features that divide between health and disease. If true, we hypothesized that artificial selective breeding for low and high aerobic exercise capacity in rats would yield animal models that contrast in propensity for development of complex disease. Here we review basic properties of a model organism to suggest that these rat models represent a more ideal substrate for mechanistic exploration of the GxE interaction between aerobic capacity and risk for complex disease.


Subject(s)
Models, Animal , Motor Activity/genetics , Obesity/genetics , Animals , Animals, Inbred Strains/genetics , Breeding , Environment , Humans , Nutrigenomics/methods , Obesity/complications , Physical Conditioning, Animal/physiology , Rats , Risk Factors , Selection, Genetic
18.
J Anim Breed Genet ; 125(5): 301-10, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18803785

ABSTRACT

The objective of this study was to test the performance of a recently proposed methodology for the estimation of realized effective size (N(e)) based on individual increase in inbreeding (DeltaF(i)) on several real pedigrees: (a) an experimental mice population; (b) a closed pedigree of fighting bulls; (c) the Spanish Purebred (SPB, Andalusian) horse pedigree; (d) the Carthusian strain of SPB pedigree; (e) the Spanish Arab horse pedigree; and (f) the Spanish Anglo-Arab horse pedigree. Several reference subpopulations were defined on the basis of generation length in order to consider only animals in the last generation, to assess the influence of the pedigree content on the estimates of N(e). The estimates of realized N(e) computed from DeltaF(i) (Ne) tended to be higher than those obtained from regression on equivalent generations. The new parameter Ne remained approximately stable when pedigree depth achieved about five equivalent generations. Estimates of take into account the genetic history of the populations, the size of their founder population, and the mating policy or bottlenecks caused by poor use of reproducing individuals. The usefulness of the realized N(e) computed from individual increase in inbreeding in real pedigrees is also discussed.


Subject(s)
Animals, Inbred Strains/genetics , Inbreeding , Pedigree , Animals , Cattle , Crosses, Genetic , Female , Male , Mice , Models, Genetic
19.
Int Immunol ; 20(6): 719-28, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18381352

ABSTRACT

Previous studies have indicated that the NZW, DBA/1, 129/sv and BUB strains are particularly sensitive to experimental anti-glomerular basement membrane (GBM)-induced immune nephritis. The present study extends previous observations by examining eight additional inbred mouse strains for their susceptibility to immune nephritis. Unlike the ALR/Lt, CAST/Ei, DDY/JclSidSeyFrk, FVB/NJ, PERA/Ei, SB/Le and BALB/c strains, the C58 mouse strain was observed to be particularly susceptible to experimental immune nephritis, with CBA mice being a close second. In contrast to the other strains, C58 mice uniformly developed heavy proteinuria, azotemia and severe glomerulonephritis with prominent crescent formation and tubulointerstitial nephritis following challenge with anti-GBM sera. These differences were associated with increased murine Ig deposition, leukocyte infiltration and IFN-gamma production within the kidneys of C58 mice. Studies aimed at elucidating the genetic factors and molecular pathways responsible for the enhanced renal disease in C58 mice are warranted.


Subject(s)
Animals, Inbred Strains/genetics , Anti-Glomerular Basement Membrane Disease/genetics , Animals , Anti-Glomerular Basement Membrane Disease/immunology , Antibodies, Heterophile/administration & dosage , Antibodies, Heterophile/immunology , Antibodies, Heterophile/metabolism , Autoantibodies/immunology , Autoantibodies/metabolism , Female , Genetic Predisposition to Disease , Immunization, Passive , Immunohistochemistry , Interferon-gamma/metabolism , Kidney/metabolism , Kidney/pathology , Mice , Proteinuria/immunology , Proteinuria/pathology , Rabbits , Species Specificity
20.
Sanid. mil ; 63(3): 240-241, jul.-sept. 2007. ilus
Article in Spanish | IBECS | ID: ibc-87011

ABSTRACT

La consanguinidad como método de cría se utiliza desde tiempos remotos, su principal inconveniente es la disminución de la capacidad de adaptación y supervivencia de los individuos con alta tasa de consanguinidad. Se realiza un estudio de la evolución de la consanguinidad de la cabaña equina de Pura Raza Española (PRE) con origen en la Yeguada Militar en comparación con la de la cabaña nacional desde el año 1970. Se detecta una sintonía entre ambas poblaciones (AU)


No disponible


Subject(s)
Animals , Horses/genetics , Consanguinity , Reproduction/genetics , Animals, Inbred Strains/genetics , Inbreeding
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