An X chromosome-linked mouse mutant (gene symbol, mdx) has been found that has elevated plasma levels of muscle creatine kinase and pyruvate kinase and exhibits histological lesions characteristic of muscular dystrophy. The mutants show mild clinical symptoms and are viable and fertile. Linkage analysis with four X chromosome loci indicates that mdx maps in the Hq Bpa region of the mouse X chromosome. This gives a gene order of mdx-Tfm-Pgk-1-Ags, the same as for the equivalent genes on the human X chromosome.There are two major forms of X chromosome-linked muscular dystrophy in man: Duchenne (McKusick number, 31020) and Becker (McKusick number, 31010) (1-3); recent linkage analyses with restriction fragment-length polymorphisms suggests that they could be allelic (4, 5). For neither of these syndromes is the primary lesion or a homologous animal model known. Several mouse mutants exhibit myopathies (6, 7); the most investigated of these are the autosomal dy and dy2 mutants (6). There is, however, controversy over whether the dy mutants are myogenic or neurogenic in origin (8-10) and, therefore, their suitability as animal models of Duchenne/Becker muscular dystrophy (11).Therefore, it is of considerable interest that a spontaneous mutation (mdx) arose in our inbred C57BL/10 colony of mice that is X chromosome-linked and produces viable homozygous animals that have high serum levels of muscle enzymes and exhibit histological lesions similar to human muscular dystrophy.MATERIALS AND METHODS Animals. C57BL/lOScSn inbred mice were originally obtained from M. Festing (MRC Laboratory Animals Centre, Carshalton, Surrey, U.K.) and further inbred for five generations prior to the spontaneous appearance of the X chromosome-linked muscular dystrophy (mdx) mutation. Segregation analysis was performed on animals within this stock. The position of mdx on the X chromosome was located by crossing to four mutants: Mottled-blotchy (Moblo), Tabby (Ta), sparse-fur (spf) and Hypophosphataemia (Hyp) (all the gift of M. Lyon, MRC Radiobiology Unit, Harwell, Oxon, U.K.).Enzyme Assays. Pyruvate kinase (PK; EC 2.7.1.40) activity was determined by a semiautomated enzyme assay (12) and expressed as urmol/min per ml of whole blood ± SEM. In some experiments the blood was fractionated into plasma and erythrocytes after withdrawal by heart puncture into heparinized tubes. The blood was centrifuged at 1,000 x gavg for 15 min, and the plasma was withdrawn; the leukocyte and interface layers were discarded, and the erythrocytes were resuspended twice in 0.15 M NaCl and recentrifuged and then were lysed in 0.05 M Tris, 7.4/1 mM EDTA/1 mM dithiothreitol/0.1% Triton X-100. Cellulose acetate electrophoresis and staining of creatine kinase (EC 2.7.3.2) was performed according to the protocol provided by Helena Laboratories (Beaumont, TX).Histology. All mice were examined clinically before being killed, and as many muscles as possible were surveyed. Ether-killed mice were skinned, eviscerated, fixed in 10% Formal/saline, halved in the median...
A genome-wide quantitative trait locus (QTL) analysis was performed in a polygenic obesity mouse model resulting from a long-term selection experiment. The parental lines were outbred lines divergently selected for 53 generations for high-fat (fat, F line) or low-fat (lean, L line) percentage (fat%) that differed fivefold in fat% at 14 weeks of age. An F2 population of 436 mice was used for the QTL analysis with 71 markers distributed across the genome. The analysis revealed significant QTLs Fob1 (for F-line obesity QTL 1), Fob2, Fob3, and Fob4, on Chromosomes (Chrs) 2, 12, 15, and X, respectively. None of these QTLs map to regions of known single gene obesity mutations (Lepob, Leprdb, Cpefat, Ay, tub), though they map to regions of previously described obesity QTLs and candidate genes. The effects of Fob1, Fob3, Fob4 were additive, and that of Fob2 was dominant. Fob2 also showed a significant female-specific effect. Fob1, Fob2, Fob3, and Fob4 explained 4.9%, 19.5%, 14.4%, and 7.3% of the F2 phenotypic variance for fat%, respectively. This study identified four loci that contributed to the response to divergent selection and control a significant proportion of the difference in obesity between the F and L lines.
Spin-label studies were carried out on Neurospora mitochondria under in vivo and in vitro labeling conditions. A long-chained spin-labeled fatty acid was incorporated by Neurospora and was found in mitochondrial phospholipids. The molecular motion at various temperatures was different from that for the same spin label under in vitro labeling conditions. The results for spin-labeled mitochondria were compared with those from isolated lipids and with those from aggregates of spin-labeled fatty acid and isolated bovine serum albumin. These comparisons suggest that the hydrocarbon portions of membranes are relatively fluid and are not extensively restricted in motion by association with proteins.
Human minisatellite probes cross-hybridize to mouse DNA and detect multiple variable loci. The resulting DNA "fingerprints" vary substantially between inbred strains but relatively little within an inbred strain. By studying the segregation of variable DNA fragments in BXD recombinant inbred strains of mice, at least 13 hypervariable loci were defined, 8 of which could be regionally assigned to mouse chromosomes. The assigned loci are autosomal, dispersed and not preferentially associated with centromeres or telomeres. One of these minisatellites is complex, with alleles 90 kb or more long and with internal restriction endonuclease cleavage sites which produce a minisatellite "haplotype" of multiple cosegregating fragments. In addition, one locus shows extreme germ-line instability and should provide a useful system for studying more directly the rates and processes of allelic variation of minisatellites.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.