| First Author | Grant S | Year | 1988 |
| Journal | Mouse News Lett | Volume | 80 |
| Pages | 181 | Mgi Jnum | J:14280 |
| Mgi Id | MGI:62451 | Citation | Grant S, et al. (1988) Mapping of mdx and Dmd. Mouse News Lett 80:181 |
| abstractText | Full text of MNL contribution: Mapping of mdx and Dmd. Our previous study mapping the mdx locus on the mouse X chromosome (MNL 72:120) has now been expanded to include a total of 778 progeny informative at the flanking markers Hprt and Pgk-1. Our new data confirms the map order Hprt-mdx-Pgk-1, with map distances for Hprt-mdx of 13.2+/-1.2cM and mdx-Pgk-1 of 14.4+/-1.3cM. An interstitial region of the X chromosome from the congenic parent of these mice is derived from the C3H/HeHa inbred strain, and carries variant alleles for the Cf-8 and Rsvp gene loci distinguishable from alleles in C57BL/lOSn.mdx by Southern analysis. A total of 34 backcross animals shown to be recombinant between Hprt and Pgk-1 were examined for segregation of these new markers. Thus far, no recombination has been observed between the Cf-8 and Rsvp loci in 271 informative backcross progeny from three different studies. Similarly, no recombination was found between these markers in any of the 34 recombinants in this study, or the equivalent of a further 305 backcross progeny. Furthermore, there was no recombination between mdx and Cf-8/Rsvp among 15 animals recombinants between Hprt and mdx. Of 19 recombinants between mdx and Pgk-1, 5 are recombinant between mdx and Cf-8/Rsvp. Thus, the Cf-8/Rsvp gene cluster lies 3.0+/-1.3cM distal to mdx. Using a murine cDNA homologous to the human gene for Duchenne muscular dystrophy, we have followed segregation of this locus in three series of interspecific backcross animals:(C57BL/6JRos x M. spretus) x C57BL/6JRos; (C57BL/6JRos x M. musculus) x CS7BL/6JRos; and(C57BL/lOSn.mdx x M. spretus) x C57BL/lOSn.mdx. From an examination of mouse-human homology, one would expect the murine Dmd locus to be very close to the centromere, tightly linked with the Otc locus as it is in man. Our mapping data, however, localized Dmd to the central region of the chromosome, far distal to Otc, indicating these loci have been separated by chromosomal rearrangements since the evolutionary divergence of mouse and man. Moreover, this localization of Dmd places it in the same region of the chromosome as mdx, suggesting the possibility that mdx is the mouse homologue of human Dmd. Further analysis, however, demonstrates that Dmd in fact lies distal to Cf-8 andRsvp, with three recombinants out of 230 animals scored for a recombination frequency of 1.3+/-0.7. If Dmd is distal to Cf-8/Rsvp, and Cf-8/Rsvp is distal to mdx, then the two loci have been effectively separated and are distinct loci on the mouse X chromosome. This is confirmed in the subset of backcross animals segregating for both mdx and Dmd. Out of 68 progeny scored for both loci, one animal recombinant between mdx and Cf-8/Rsvp has been confirmed as recombinant between mdx and Dmd. Thus, these data allow for the fine mapping of two distinct loci for recessive muscular dystrophy on the mouse X chromosome. (Grant, L Mullins, Stephenson and Chapman) |
