| First Author | Sweet HO | Year | 1994 |
| Journal | Mouse Genome | Volume | 92 |
| Issue | 3 | Pages | 526-28 |
| Mgi Jnum | J:20792 | Mgi Id | MGI:68862 |
| Citation | Sweet HO, et al. (1994) Proportional dwarf (pdw), a new recessive mutation on mouse Chromosome 8. Mouse Genome 92(3):526-28 |
| abstractText | Full text of Mouse Genome contribution: PROPORTIONAL DWARF (pdw), A NEW RECESSIVE MUTATION ON MOUSE CHROMOSOME 8. H.O. Sweet, S.A. Cook, P. Ward-Bailey and K.R. Johnson; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609 USA. Proportional dwarf (pdw), a recessive mutation, arose on the DBA/2J inbred strain in 1991 and is being maintained on that strain background in the Mouse Mutant Resource of The Jackson Laboratory. The homozygous mutant is characterized by shortened limbs, tail, head, and body. This phenotype is similar to that of several previously described mutants, including brachymorphic (bm), achondroplasia (cn), stubby (stb), and rich (tch). The bm, cn, and stb mutations have been described by M.C. Green (1) and the tch mutation by Archer et al. (2). Homozygotes, pdw/pdw, are classified and weaned at twenty-five days of age. Both sexes are viable and fertile, although males are preferentially used in matings. There is some mortality among homozygotes prior to weaning. The mutation is maintained in forced heterozygosity by sibling mating on the DBA/2J background. Data in Table 1 are from matings on this background. Table 1. Recessive inheritance of pdw. Female: +/pdw; Male: +/pdw; +: 79; pdw: 26; Total: 105; X2: .0032. Female: pdw/pdw; Male: +/pdw; +: 53; pdw: 37; Total: 90; X2: 2.8444. Female: +/pdw; Male: pdw/pdw; +: 89; pdw: 65; Total: 154; X2: 3.7402. Female: +/+; Male: pdw/pdw; +: -; pdw: 18; Total: 20; X2: -. Female: pdw/pdw; Male: pdw/pdw; +: 20; pdw: -; Total: 18; X2: -. A pdw/pdw male was outcrossed to a C57BL/6J female and the resulting Fl hybrids were intercrossed. Data from this intercross confirmed that the mutation is recessive and segregates normally: + 229, pdw 59 (N=289, X2 = 3.13). Genetic linkage was determined by analysis of this same intercross. All affected F2 mice (pdw/pdw) were typed for isoenzyme differences between DBA/2J and C57BL/6J. Linkage was initially found with Esl on Chromosome 8 (Chr 8). To better position the pdw mutation on Chr 8 two microsatellite markers, D8Mit8 and D8Mit33, were typed by PCR amplification. Gene order and recombination frequencies were calculated using the MapManager computer program (3) which minimizes the number of obligate crossover events. The results of this analysis are shown in Fig. 1. Fig. 1. (Legend). Genetic map position of pdw on Chr 8. 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). Individual mouse genotypes at all four loci typed on Chr 8 in this cross have been deposited as a MapManager file in the Mouse Genome Database, Accession Number MGD-CREX- 151. Allele tests with mutations of similar phenotype were negative. Additional allele tests with another as yet unnamed mutant gene mapping to the same position on Chr 8 and myd (myodystrophy) were also negative. One pdw/pdw male adult breeder exhibited a myopathy similar to myd. This condition has not proved to be genetic nor has it been observed in other comparably aged pdw/pdw of either sex. Dr. James R. Archer and colleagues, Bone and Joint Research Unit, London Hospital Medical College, compared pdw with tch histologically and found no similar lesions. In particular there was no indication of the disruption at the center of the growth plate or remnants of non-calcified cartilage typical of tch. Dr. Sandy Marks, Department of Cell Biology, University of Massachusetts Medical Center, examined growth plates and mineralization patterns in the skeletons of pdw/pdw and littermate +/pdw controls at 45 and 50 days of age. Other than radiographic evidence that these are proportional dwarfs (pdw/pdw), he could find no abnormalities. Illustrated in Fig. 2 are skeletons from a homozygous pdw/pdw and littermate +/pdw control at 50 days of age. Fig. 2. (Legend). Radiographs comparing skeletons from a homozygous pdw/pdw mouse (top) with a heterozygous +/pdw littermate control (bottom) at 50 days of age. Acknowledgments We thank Joseph Nadeau and Linda Washburn for reviewing the manuscript before submission. This work was supported by National Science Foundation Grant BIR-8915728 and National Institutes of Health Grant CA 34196. References 1. Green, M.C. (1989) In: Genetic Variants and Strains of the Laboratory Mouse, M.F. Lyon and A.G. Searle, Eds, pp. 12-404, Oxford University Press. 2. Archer J.R. et al. (1991) Genet Res 57:29-35. 3. Manly, K.M. (1993) Mamm Genome 4: 303-313. |
