Phenotypic differences on the outcome of the host-parasite relationship: behavior of mice of the CBi stock in natural and experimental infections.

Investigation of defined animal models may help to elucidate the role of the host genetic background in the development and establishment of a parasitic infection. Four lines of mice obtained by disruptive selection for body conformation (CBi+, CBi-, CBi/C and CBi/L) and the unselected control line CBi were examined in their response to different parasites to assess whether these distinct genotypes showed differences in their resistance to natural and experimental parasitosis. Protozoans (Trichomonas muris and Spironucleus muris) and nemathelminths (Syphacia obvelata and Aspiculurus tetraptera) were found naturally parasitizing the mice's intestines. CBi/C and CBi were the only genotypes in which T. muris was found. CBi- was least resistant to S. muris. The helminth parasitic burden showed differences between sexes within genotypes (males had a higher burden than females) and among genotypes (CBi/L males had the lowest burden). CBi/L animals were also most resistant to experimental challenge with Heligmosomoides polygyrus and Trypanosoma cruzi. Since all the animals examined shared a common habitat throughout the study and were equally exposed to infection, the phenotypic differences in the natural enteroparasitism herein described evince genetic differences among lines in the host-parasite relationship. This interpretation is further supported by the differences in the response to the experimental challenge to H. polygyrus and T. cruzi.

Muscle-bone relationships in mice selected for different body conformations.

Some muscle-bone relationships were studied in terms of gastrocnemius muscle weight, femur and tibia length and femur and tibia weight in four lines of mice (CBi-, CBi+, CBi/L and CBi/C) artificially selected for different body conformations and in the unselected control line (CBi). CBi- (low body weight--short tail) and CBi+ (high body weight--long tail) lines were divergently selected following the positive genetic correlation between body weight and tail (skeleton) length (agonistic selection). In contrast, CBi/L (low body weight--long tail) and CBi/C (high body weight--short tail) were also divergently selected but against the aforementioned correlation (antagonistic selection). The relationship between bone length and muscle weight was interpreted based on the assumption that the increased tension generated by the longitudinal growth of a bone, brings about an increase in the mass of the muscles attached to it. All CBi+, CBi/C and CBi/L mice showed enlarged femurs and tibias, but only those genotypes simultaneously selected for high body weight (CBi+ and CBi/C) showed heavier muscles than controls. The CBi+ and CBi- genotypes with agonistic selection differ in bone length and muscle weight, as it would be expected of the allometric modification of their body conformation, showing the associated longitudinal bone growth-muscle growth. CBi/C and CBi/L mice, with a non-allometric modification of body conformation, exhibited the same bone length but different muscle weight. Consequently, the antagonistic criterion allowed to confirm that the genetic influence on of the proposed muscle-bone relationships could be modified, thus making it possible to lengthen the bone through selection of a long skeleton and to avoid the correlated effect on muscle mass, by selecting for a low body weight, bringing forth presumptive evidence that both processes were genetically independent.

Body weight and egg weight dynamics in layers.

The association between body weight-age and egg weight-age patterns was studied in a segregating population of laying hens belonging to the F3 generation of a Rhode Island Red x White Leghorn reciprocal cross. Body weight and egg weight were expressed as a function of time using the model developed by Weatherup and Foster. Each hen was characterized in terms of its asymptotic body weight (ABW), maturing rate for body weight (MBW), asymptotic egg weight (AEW), and maturing rate for egg weight (MEW) values. Four groups of hens were distinguished by means of a principal component analysis. Birds belonging to Groups 1 and 3 were discriminated for their egg weight-age pattern. Group 1 included hens laying the heaviest eggs (AEW = 66.1 g) at the lowest maturing rate (MEW = 0.922), the inverse being true for birds in Group 3 (AEW = 55.7 g and MEW = 0.737). Birds belonging to Groups 2 and 4 were distinguished for their body weight-age pattern. Hens in Group 2 showed the lowest ABW (1,893 g) and MBW (0.764) whereas the heaviest (ABW = 2,802 g) and less mature (MBW = 0.929) birds were found in Group 4. The results confirm the partial pleiotropic basis of the body weight-egg weight correlation, evincing the feasibility of applying selective pressure not only on each character separately but also on maturing rate independently of asymptotic weight within each trait. This strategy could be implemented using a biological selection index based on principal component analysis equations.

Morphometric skeletal traits, femoral measurements, and bone mineral deposition in mice with agonistic selection for body conformation.

Morphometric skeletal traits, femoral histomorphometry, and bone mineral deposition were investigated in two lines of mice (CBi+ and CBi-) divergently selected for body conformation (CBi+: high body weight, long tail; CBi-: low body weight, short tail) and in the unselected control line CBi. Linear morphometric measurements, absolute and relative skeletal weights, absolute and relative femoral weights, and total biomass sustained per unit of total or tail-less skeletal weight were increased in CBi+ mice in comparison with controls. This greater biomass implies a greater mechanical demand that is satisfied by a heavier skeleton. Looking specifically to the femur, CBi+ mice had heavier bones, both absolute and relative, with a greater diameter and a greater cortical thickness, resulting in a greater cortex/diameter ratio than controls. Although morphometric measurement and absolute skeletal weight were lower in CBi- than in CBi mice, the relative skeleton weight and the biomass sustained per unit of skeletal weight were not modified in the downward selection line when compared with controls. Therefore, CBi- mice did not exhibit a greater mechanical demand as CBi+ mice did. These results led us to consider at least three main aspects: bone length growth; cortical thickness/bone diameter ratio; and bone calcification. The long bones appeared to have a genetically determined predisposition to achieve a given length, which, however, could be modified by artificial selection. Cortical thickness would be directly related to the biomass sustained. This variable increased in CBi+ mice, a genotype that supports a greater biomass than controls, and did not change in CBi- mice, which sustained the same biomass as CBi. The pattern of mineral deposition did not accompany the functional demand because it was higher in CBi- than in CBi+; however, as artificial selection separately affected bone material quality and bone architectural design, these genotypes could express architectural modifications that override any change in bone material quality.

Angiogenesis induced by tumor-host interaction in the rat.

There is a clear-cut cause-effect relationship between vascularization of a given tumor and its capacity to disseminate and metastasize. Hence, it is very important to study the contribution of the two main factors determining the generation of new blood vessels namely the tumor and the host where it grows. The influence of the tumor-host interaction on the induction of angiogenesis was studied in a tumor model-system composed by two lines of rats selected for resistance or susceptibility to a sarcoma (S-E100) and two transplantable tumors: Sarcoma E 100 and Lymphoma TACB. One line is resistant to the sarcoma but susceptible to the lymphoma while the other line behaves in the opposite way. Studying the angiogenesis generated by the s.c. implantation of each tumor in two different hosts we found that the same tumor induced different angiogenic responses according to the host in which it is growing and that the same host shows a different response according to the tumor with which it is challenged, suggesting that tumor-host interactions determine the intensity of the neovascularization process.

Long-bone biomechanics in mice selected for body conformation.

Two lines of mice divergently selected from the control strain (CBi) against the positive phenotypic correlation between body weight (b.w.) and tail (skeletal) length were obtained (CBi/C: high weight, short tail; CBi/L: low weight, long tail). The selected animals showed a different relationship between body and skeletal masses. To compare the adequacy between biomass and load-bearing ability of the skeleton, and to describe the eventual role of bone mechanostat in the production of these changes, cross-sectional and bending properties of both femur diaphyses were determined in CBi, CBi/C, and CBi/L adult mice of both genders. Cortical bone material quality (elastic modulus) was reduced in the selected lines (p < 0.001), significantly less in CBi/C than in CBi/L. In contrast, cross-sectional design (b.w.-adjusted values of moment of inertia, CSMI) was largely improved (p < 0.001), significantly more in CBi/C than in CBi/L. These effects determined a greater stiffness and strength in CBi/C than in CBi/L or CBi weight-paired mice. The elevations of the negative regression lines between elastic modulus and CSMI ("distribution/quality" curves) decreased in the order CBi/C > CBi/L > CBi. Data show that selection improved diaphyseal stiffness and strength in CBi/C animals because of an architectural overcompensation for the reduced bone material quality. Therefore, an inadequate control of long-bone architectural design as a function of the mechanical quality of cortical bone and b.w. bearing could have been induced in that line. Assuming bone mechanostatic regulation to be genetically programmed, some of the corresponding biological determinants should be transmitted independently, because artificial selection separately affected material quality and architectural design. The possibility of transmission of an inadequate mechanostatic function (inability to adapt bone modeling to bone material quality as a function of the biomass to be supported) was also shown, as some genotypes could express architectural modifications that largely exceed bone material quality deterioration.

Bone mineral deposition in mice selected for body conformation.

Bone mineral content was investigated in 2 lines of mice (CBi/C and CBi/L) that carry different biomasses per unit of skeletal weight. These lines also differ in their femoral histomorphometry and bone biomechanics. The logarithmic form of the allometric equation describing the relationship between ash weight and body weight was used to compare the mineral content in both sexes of these genotypes. No statistical difference was observed in the slopes of the curves describing the changes in bone mineral content as a function of age. Both lines had greater values than the line for control animals. The selected lines did differ significantly in the intercepts of the curves on the y-axis. An independent determination of both allometric parameters by genetic factors is proposed. Genes or groups of genes could affect mineral deposition in two ways: one could produce positional changes of the allometric curves in the embryo but leave their postnatal slopes unchanged; another could modify the postnatal slope of the curve. The combined expression of these different genes should be important in preserving homeostatic functioning of the organism.

Morphometric traits and femoral histomorphometry in mice selected for body conformation.

Skeleton characteristics and femoral histomorphometry were investigated in two lines of mice divergently selected for antagonistic conformations (CBi/C: high body weight-short tail; CBi/L: low body weight-long tail). An unselected control line (CBi) was used. Genotypes were a significant source of variation for almost all traits studied (body size, skeletal measurements, histomorphometry of the femur, number of caudal vertebrae) indicating that eighteen generations of artificial selection were successful in modifying phenotypes. Antagonistic selection revealed an association between the mechanisms that regulate skeleton growth and body conformation. Trunk length seemed to be dependent of the biomass a mouse would attain. Femur length and its morphometric characteristics were conditioned by other factors than body weight. The observed response in caudal vertebrae number could be explained if this character is considered as a threshold one. The selective procedure applied in this research was also useful to study other biological characters such as fat deposition, immune reactions and bone biomechanics.

[Influence of host genotype in the development of metastasis in a transplantable lymphoma in rats]. / Influencia del genotipo del huésped en la formación de las metástasis de un linfoma transplantable de rata.

For the purpose of investigating the influence of the host genotype in the metastatic process, the frequency of lymph nodes metastases of a transplantable rat lymphoma (L-TACB) in relation to tumor growth and to capacity of rejection was studied in the inbred lines m, eR and eS and in the F1 hybrids m x eR, m x eS and eR x eS. L-TACB is a spontaneous poorly differentiated lymphoma that appeared in the peritoneal cavity of a rat of the inbred line e; since 1969 it has been maintained by subcutaneous grafting in e rats. The tumor was inoculated by trocar and measured with a caliper every 3 to 4 days, the size expressed in mm2 (large diameter x minor diameter). Percentages of takes, regression, lethality and axillary and/or inguinal lymph nodes metastases were registered. The maximum size (TMx) reached by the primary tumor, in animals with (TMx-CM) and without metastasis (TMx-CM) were recorded. Tumor size (TMx) in animals of line m was greater (p less than 0.01) than in rats of subline eR while tumor regression was significantly less in eR (29.7%) than in m (72.7%) and eS (100%) (p less than 0.001), suggesting that tumor growth rate was independent of the capacity of tumor rejection. Rats of genotypes m and eS had a great capacity of tumor rejection; however, the hybrid m x eS showed a low percentage of regression (17.2%) (p less than 0.001). This result reveals an opposite effect produced by the genetic interaction of the m and eS parental lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth analysis in two lines of rats and their reciprocal F1 crosses under two nutritional environments. Heterosis for body weight and maturing rate.

The heterotic effects for body weight during the early postweaning period and on the von Bertalanffy growth equation parameters in relation with the growth pattern as a whole were investigated in rats with caloric restriction (20%) and in controls with ad libitum feeding. Body weight at fixed ages, weight-age curves, asymptotic weight, mature size and maturing curves were evaluated in a cross between two highly inbred lines of rats. Growth curve parameters were combined in a single value by the multivariate method of principal components in order to characterize the particular growth pattern of each group. Positive and significant heterotic effects for body weight were observed suggesting the presence of non-additive genetic variation for this trait. Additivity was an important source in asymptotic size. An heterotic response was observed in mature rate showing a dominant deviation towards high values of this character. Caloric restriction diminished body weight, but asymptotic size was not modified. Maturity was affected along the period studied. Hybrids reached an intermediate asymptotic weight in relation to parental lines exhibiting greater maturity in the prepuberal period. It is suggested that in livestock production crossbreeding will be profitable if additivity for asymptotic weight and dominance deviation for maturing rate could be combined in the F1 hybrid. Maternal breed should be lighter and mature more rapidly than the paternal one if maintenance costs of the breeding stock and growing potentiality of the crossbred progeny are considered.

Influencia del genotipo del huésped en la formación de las metástasis de un linfoma transplantable de rata. / [Influence of host genotype in the development of metastasis in a transplantable lymphoma in rats]

For the purpose of investigating the influence of the host genotype in the metastatic process, the frequency of lymph nodes metastases of a transplantable rat lymphoma (L-TACB) in relation to tumor growth and to capacity of rejection was studied in the inbred lines m, eR and eS and in the F1 hybrids m x eR, m x eS and eR x eS. L-TACB is a spontaneous poorly differentiated lymphoma that appeared in the peritoneal cavity of a rat of the inbred line e; since 1969 it has been maintained by subcutaneous grafting in e rats. The tumor was inoculated by trocar and measured with a caliper every 3 to 4 days, the size expressed in mm2 (large diameter x minor diameter). Percentages of takes, regression, lethality and axillary and/or inguinal lymph nodes metastases were registered. The maximum size (TMx) reached by the primary tumor, in animals with (TMx-CM) and without metastasis (TMx-CM) were recorded. Tumor size (TMx) in animals of line m was greater (p less than 0.01) than in rats of subline eR while tumor regression was significantly less in eR (29.7

) than in m (72.7

) and eS (100

) (p less than 0.001), suggesting that tumor growth rate was independent of the capacity of tumor rejection. Rats of genotypes m and eS had a great capacity of tumor rejection; however, the hybrid m x eS showed a low percentage of regression (17.2

) (p less than 0.001). This result reveals an opposite effect produced by the genetic interaction of the m and eS parental lines.(ABSTRACT TRUNCATED AT 250 WORDS)

[Inheritance of susceptibility to tumors and metastases in rodents]. / Herencia de la susceptibilidad a los tumores y a las metástasis en roedores.

The behavior of two spontaneous transplantable rat tumors and a mouse lymphoma was studied in different hosts. A resistant (eR) subline to Sarcoma E 100 (S-E 100) and a susceptible one (eS) were obtained by divergent selection carried out in an inbred line of rats IIM (e). The phenotypic frequencies of the resistant and susceptible individuals to S-E 100 in the base population e and eR, eS, F1 and F2 fitted with the theoretical frequencies of a model of two independent pairs of genes, one (T) with complete dominance (locus SE1) and the other (R) with partial dominance (locus SE2). Locus SE2 would regulate the antitumoral response. Resistance to S-E 100 was found to be a dominant trait. The subcutaneous challenge of eR and eS rats with Lymphoma TACB (L-TACB) showed a different behavior. Subline eR (resistant to S-E 100) was susceptible to L-TACB while subline eS (susceptible to S-E 100) was resistant. A tumor-host interaction was found, revealing that genotypes resistant to S-E 100 were susceptible to L-TACB; in addition, susceptible animals (eR) developed lymph node metastases. It was observed, using animals of different genotypes, that susceptibility to L-TACB metastases and to local tumor growth, would be conditioned by different genes. Delayed type hypersensitivity (DTH) to tumor antigens (S-E 100 and L-TACB) and humoral immune response and DTH to sheep red blood cells (SRBC) were investigated in eR and eS rats. Differences between both sublines were statistically significant suggesting that genes involved in the divergent selection would regulate the antitumoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

Herencia de la susceptibilidad a los tumores y a las metástasis en roedores. / [Inheritance of susceptibility to tumors and metastases in rodents]

The behavior of two spontaneous transplantable rat tumors and a mouse lymphoma was studied in different hosts. A resistant (eR) subline to Sarcoma E 100 (S-E 100) and a susceptible one (eS) were obtained by divergent selection carried out in an inbred line of rats IIM (e). The phenotypic frequencies of the resistant and susceptible individuals to S-E 100 in the base population e and eR, eS, F1 and F2 fitted with the theoretical frequencies of a model of two independent pairs of genes, one (T) with complete dominance (locus SE1) and the other (R) with partial dominance (locus SE2). Locus SE2 would regulate the antitumoral response. Resistance to S-E 100 was found to be a dominant trait. The subcutaneous challenge of eR and eS rats with Lymphoma TACB (L-TACB) showed a different behavior. Subline eR (resistant to S-E 100) was susceptible to L-TACB while subline eS (susceptible to S-E 100) was resistant. A tumor-host interaction was found, revealing that genotypes resistant to S-E 100 were susceptible to L-TACB; in addition, susceptible animals (eR) developed lymph node metastases. It was observed, using animals of different genotypes, that susceptibility to L-TACB metastases and to local tumor growth, would be conditioned by different genes. Delayed type hypersensitivity (DTH) to tumor antigens (S-E 100 and L-TACB) and humoral immune response and DTH to sheep red blood cells (SRBC) were investigated in eR and eS rats. Differences between both sublines were statistically significant suggesting that genes involved in the divergent selection would regulate the antitumoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS)