| First Author | Lane PW | Year | 1994 |
| Journal | Mouse Genome | Volume | 92 |
| Issue | 4 | Pages | 686-687 |
| Mgi Jnum | J:22093 | Mgi Id | MGI:69984 |
| Citation | Lane PW, et al. (1994) Shimmy (shmy), a new mutation on Chromosome 14 of the mouse. Mouse Genome 92(4):686-687 |
| abstractText | Full text of Mouse Genome contribution: SHIMMY (shmy), A NEW MUTATION ON CHROMOSOME 14 OF THE MOUSE. Priscilla W. Lane, Susan A. Cook, Roderick T. Bronson, Kenneth R. Johnson, and Muriel T. Davisson. The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA In June of 1991 a mutation with an abnormal gait arose at generation F7 in a non-inbred stock carrying the mutation skeletal fusions with sterility, sks (1). [The mutation sks arose on the A/J strain and was crossed to the hybrid B6C3Fe-a/a prior to brother x sister breeding with selection for the non-agouti brown (a/a b/b) phenotype.] Two mice, a male and female, with wobbly gaits were among the six offspring in the first litter from a normal appearing pair of untested sks breeders. Each wobbly gaited mouse was mated to a normal appearing sibling. The affected male did not breed; the affected female produced five litters. Of the 22 mice in the five litters, 12 had abnormal gaits and 10 were normal. This ratio suggested that the sibling used as the sire was a heterozygous carrier and that the new mutation was recessive with full penetrance. In addition, breeding data for the first year of pair matings of affected (homozygous) females x carrier (heterozygous) males produced 171 offspring, 89 normal and 82 affected (48%, X2=0.29) showing the expected segregation for a recessive gene. Fl hybrids produced by outcrossing affected mice with mice from other strains never showed the mutant phenotype, confirming the recessive nature of this mutation. Homozygotes have a hesitant and wobbly gait that is evident at 12-14 days of age. They are also slightly smaller than unaffected littermates. One or both eyes sometimes remained closed until 15-20 days of age; however, the eyes appear normal once opened. Affected mice attain close to normal size but maintain a very wobbly gait that is most evident in the hind quarters that sway from side to side. Because of this gait, the mutation has been called shimmy (shmy). To date no homozygous shimmy male has bred. Testes from two homozygotes and two controls were examined histologically and testes from the affected mice could not be distinguished from the controls. In addition, the vas deferens were stripped and sperm from two affected mice and a control were observed. Sperm from the shmy/shmy mice had normal heads and tails and were plentiful and motile. Six mutant and four control mice were deeply anesthetized and fixed by intravascular perfusion of Bouin's solution. Multiple paraffin sections of brain and spinal cord from three mutants and three controls were stained with hematoxylin and eosin (H&E). Replicate sections were stained with luxol fast blue and cresyl violet (LFB-CV). Similar sections of legs, including muscle and nerve, were prepared from two eight-month-old mutants. The entire hind groin of one eight-month-old shimmy mouse was serially sectioned and alternate strips of sections were stained with H&E and LFB-CV. The only lesions observed in mutant mice and not in controls were a few dystrophic axons in the lateral nucleus of the cerebellum. Apart from this mild abnormality, all tissues observed were normal. These histopathologic examinations did not reveal the cause of the neurological phenotype of the mutant mice. To find the chromosomal location of shmy, segregation was examined in F2 progeny from an intercross of Fl hybrids between a homozygous shimmy female and a CAST/Ei (M.m. castaneus) male. Affected F2 mice (shmy/shmy) were saved and tissues were taken for isozyme and DNA analysis. Linkage was initially found with nucleoside phosphorylase-1 (Npl) on Chromosome 14. There were four recombinants between shmy and Npl among the 36 chromosomes of the first 18 mice typed, giving an estimated recombination of 11%. To confirm this linkage and refine the map position of shmy, additional shmy/shmy F2 mice and additional Chr 14 markers were examined. A total of 50 affected F2 mice were typed for Npl by isozyme analysis and for D14Mit43 and D14Mit45 by PCR analysis. The gene order and recombination frequencies shown in Fig. 1 were calculated using the Map Manager computer program (2) which minimizes the number of obligate crossover events. The haplotypes of individual mice for all four Chr 14 loci typed in this cross have been deposited as a Map Manager file in the Mouse Genome Database, Accession Number MGD-CREX-182. These data place shmy at the proximal end of mouse Chr 14, in a region that shares conserved gene arrangements with human Chr 10q or 3p (3). No mouse mutations that produce a similar phenotype map to this region of Chr 14. Fig. 1. (Legend). Genetic map position of shmy on Chr 14. For haplotype analysis, each affected F2 progeny represents two tested chromosomes (r = number of recombinant chromosomes, N = total number of chromosomes tested, % r = percent recombination, SE = standard error of % r). Acknowledgments We thank Belinda Harris for the observation on shimmy sperm. This work was supported by NSF grant BIR8915728, NIH grant GM46697, and Cancer Core grant CA 34196. References 1. Handel M.A., Lane P.W., Schroeder A.C., and Davisson M.T. Gamete Res. 21: 409-423, 1988. 2. Manly K.F. Mamm. Genome. 4: 303-313, 1993. 3. GBASE, 1994. The Genomic Database of the Mouse maintained at The Jackson Laboratory by L.J. Maltais, D.P. Doolittle, M.T. Davisson, J.N. Guidi, and T.H.Roderick. |
