ABSTRACT
We measured levels of ob mRNA in epididymal fat pads of rats exposed to manipulations designed to alter circulating insulin and glycemia. Changes in ob mRNA were compared to alterations in GLUT-4 glucose transporter mRNA, which is known to be regulated under these conditions. 48 h fasting decreased GLUT-4 mRNA to 23% of control with restoration beginning by 6 h refeeding and full restoration at 24 h. In contrast, ob mRNA decreased less markedly to 47% of control with only partial restoration by 24 h. Two days of streptozocin (STZ)-diabetes (glucose > 400 mg/100 ml) decreased GLUT-4 mRNA to 8% of control with restoration by two days of S.C. insulin. In contrast, ob mRNA decreased to 42% of control and was not restored by insulin. Six days of insulin administration to normal rats under conditions of ad lib. feeding, but without otherwise preventing the blood glucose from decreasing, resulted in no significant change in levels of either ob or GLUT-4 mRNA.
Subject(s)
Adipose Tissue/metabolism , Blood Glucose/physiology , Diabetes Mellitus, Experimental/metabolism , Gene Expression Regulation/physiology , Insulin/blood , Muscle Proteins , Protein Biosynthesis , Animals , Base Sequence , DNA Primers , Eating , Epididymis , Fasting , Gene Expression Regulation/drug effects , Glucose Transporter Type 4 , Humans , Insulin/pharmacology , Leptin , Male , Molecular Sequence Data , Monosaccharide Transport Proteins/biosynthesis , Obesity/genetics , RNA, Messenger/analysis , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley , Recombinant Proteins/pharmacology , Reference Values , Time FactorsABSTRACT
Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant disease of unknown pathogenesis which is characterized by weakness of the face and shoulder girdle. It is associated with a sensorineural hearing loss which may be subclinical. FSHD has been mapped to the distal most portion of 4q35, although the gene has not yet been identified. Distal 4q has homology with a region of mouse chromosome 8 to which a mouse mutant, myodystrophy (myd), has been mapped. Muscle from homozygotes for the myd mutation appears dystrophic, showing degenerating and regenerating fibers, inflammatory infiltrates, central nuclei, and variation in fiber size. Brainstem auditory evoked potentials reveal a sensorineural hearing loss in myd homozygotes. Based on the homologous genetic map locations, and the phenotypic syndrome of dystrophic muscle with sensorineural hearing loss, we suggest that myd represents an animal model for the human disease FSHD.
Subject(s)
Disease Models, Animal , Hearing Loss, Sensorineural/genetics , Mice, Mutant Strains , Muscular Dystrophies/genetics , Muscular Dystrophy, Animal/pathology , Animals , Chromosome Mapping , Chromosomes, Human, Pair 4 , Evoked Potentials, Auditory, Brain Stem , Facial Muscles/pathology , Genotype , Humans , Mice , Mice, Mutant Strains/genetics , Muscle Fibers, Skeletal/pathology , Muscular Dystrophy, Animal/genetics , Necrosis , Phenotype , Regeneration , Shoulder/pathology , SyndromeABSTRACT
Myodystrophy (myd), an autosomal recessive mutation of the mouse characterized by progressive weakness and dystrophic muscle histology, maps to the central portion of Chromosome (Chr) 8 (Lane et al. J. Hered 67, 135, 1976). This portion of Chr 8 contains the genes for a mitochondrial uncoupling protein (Ucp) and kallikrein (Kal3), which map to distal 4q in the human, providing evidence for a segment of homology. Characteristics of the myd phenotype coupled with this homology suggest that myd may be a mouse homolog of facioscapulohumeral muscular dystrophy (FSHD), which maps to human 4q35. We have confirmed and expanded the region of mouse 8-human 4 homology by generating a map of Chr 8 in an interspecific backcross of C57BL/6J and a partially inbred strain derived from M. spretus. The map is comprised of the genes for Ucp, coagulation factor XI (Cfl1), and chloride channel 5 (Clc5), all of which have homologs on distal human 4q, 15 microsatellite loci, and the membrane cofactor protein pseudogene (Mcp-ps). To place myd in the genetic map, 75 affected progeny from an intersubspecific backcross of animals heterozygous for myd with Mus musculus castaneus were genotyped with Chr 8 microsatellite loci. The mutation maps between D8Mit30 and D8Mit75, an interval that is flanked by genes with human homologs at distal 4q. These results are consistent with the possibility that myd is the mouse homolog of FSHD.
Subject(s)
Chromosomes, Human, Pair 4/genetics , Chromosomes , Muridae/genetics , Muscular Dystrophy, Animal/genetics , Mutation , Animals , Base Sequence , Chromosome Mapping , Crosses, Genetic , Female , Genetic Linkage , Genetic Markers , Haplotypes , Humans , Male , Mice , Mice, Inbred Strains , Molecular Sequence DataABSTRACT
Myodystrophy (myd) is an autosomal-recessive mouse mutation with dystrophic skeletal muscle. We propose that myd may be a model of the human disorder facioscapulohumeral dystrophy (FSHD) on the basis of clinical features and homologous genetic map locations. FSHD maps to human 4q35, while myd maps to mouse chromosome 8. To explore the relationship between FSHD and myd, it is necessary to define the homologous regions of human chromosome 4 and mouse chromosome 8, and ultimately, identify the genes underlying both disorders. A kallikrein gene (Kal3) was previously mapped by in situ hybridization to mouse chromosome 8 and human 4q35. We report the genetic map location of Kal3, bringing to 4 the number of genes with homologues on human 4q31-35 placed on the genetic map of mouse chromosome 8. As a first step in gene isolation, we have narrowed the interval containing myd by typing 125 affected mice with microsatellite markers. Analysis of recombinants placed myd in an interval that is flanked by genes with homologues in human 4q.
Subject(s)
Disease Models, Animal , Mice, Mutant Strains/genetics , Muscular Dystrophy, Animal/genetics , Mutation , Rodent Diseases/genetics , Animals , Base Sequence , Chromosome Mapping , Chromosomes, Human, Pair 4 , Face , Humans , Humerus , Mice , Molecular Probes/genetics , Molecular Sequence Data , Muscular Dystrophies/genetics , Scapula , Sequence HomologyABSTRACT
Myodystrophy (myd) is an autosomal-recessive mouse mutation with dystrophic skeletal muscle. We propose that myd may be a model of the human disorder facioscapulohumeral dystrophy (FSHD) on the basis of clinical features and homologous genetic map locations. FSHD maps to human 4q35, while myd maps to mouse chromosome 8. To explore the relationship between FSHD and myd, it is necessary to define the homologous regions of human chromosome 4 and mouse chromosome 8, and ultimately, identify the genes underlying both disorders. A kallikrein gene (KaL3) was previously mapped by in situ hybridization to mouse chromosome 8 and human 4q35. We report the genetic map location of Kal3, bringing to 4 the number of genes with homologues on human 4q31-35 placed on the genetic map of mouse chromosome 8. As a first step in gene isolation, we have narrowed the interval containing myd by typing 125 affected mice with microsatellite markers. Analysis of recombinants placed myd in an interval that is flanked by genes with homologues in human 4q.
Subject(s)
Chromosome Mapping , Muscular Dystrophy, Animal , Animals , Chromosomes, Human, Pair 10 , Chromosomes, Human, Pair 4 , Chromosomes, Human, Pair 8 , Humans , Mice , Muscular Dystrophies/genetics , Muscular Dystrophy, Animal/genetics , Mutation , Restriction MappingABSTRACT
The incidence of subluxation or dislocation of the hip in 185 cerebral palsied patients was 25.4%. Posterior iliopsoas transfer will decrease hip deformities but complications such as weakness of hip flexion or abduction contracture are to be expected in some cases. Posterior iliopsoas transfer did not give uniformly satisfactory results; 9 out of 17 patients were fair to poor even combined with innominate osteotomy and/or versus derotation osteotomy of the femur. Early prophylactic surgery of lesser extent such as adductor release is desirable since treatment of established subluxation or dislocation is often unsatisfactory.
Subject(s)
Cerebral Palsy/complications , Hip Dislocation/surgery , Muscles/surgery , Casts, Surgical , Child , Child, Preschool , Evaluation Studies as Topic , Female , Follow-Up Studies , Hip Dislocation/etiology , Hip Dislocation/rehabilitation , Humans , Locomotion , Male , Osteotomy , Postoperative ComplicationsABSTRACT
Thrombocytopenic patients with surgically correctable lesions such as radial clubhands are too often repeatedly transfused with randomly pooled platelets. This is followed by a clinical rejection of the foreign protein and rapid destruction of the platelets. There may be excessive bleeding episodes. Tissue typing technics now available can provide antigenically compatible platelet concentrates which elicit few of these reactions. Therefore, multiple reconstructive procedures can be achieved with a greater safety margin than previously possible.
