| First Author | Tease C | Year | 1993 |
| Journal | Mouse Genome | Volume | 91 |
| Issue | 1 | Pages | 137-38 |
| Mgi Jnum | J:4283 | Mgi Id | MGI:52779 |
| Citation | Tease C, et al. (1993) Tail kinks, small size, and white spotting (Tks): a radiation-induced mutation onchromosome 9. Mouse Genome 91(1):137-38 |
| abstractText | Full text of Mouse Genome contribution: TAIL KINKS, SMALL SIZE, AND WHITE SPOTTING (Tks) : A RADIATION-INDUCED MUTATION ON CHROMOSOME 9. Charles Tease and Graham Fisher. MRC Radiobiology Unit, Chilton, Didcot, Oxon OX11 ORD, U.K. Introduction. In the course of an experiment to investigate radiation-induced loss of chromosome 19 [1] a small number of dominant visible mutations were found among the progeny of irradiated females. We present here a phenotypic description of one of these mutants and report data showing its chromosomal location and position. Materials and Methods. F1 hybrid C3H/HeH x 101/H female mice were given a caudal body dose of 4 Gy of acute X-rays and subsequently mated to tester males doubly heterozygous for Rb(8.19)lCt and Rb(9.19)163H. Offspring were screened for complementation of induced maternal chromosome 19 loss by paternal chromosome 19 gain and also for the occurrence of dominant visible mutations. Phenotype. The original mutant was male and had a curly tail and a reduced body size compared to littermates; at weaning it had a white patch on its thorax. Of 93 offspring (18 litters, mean = 5.2) sired by this male in matings with Fl hybrid females, 33 had a tail kink at birth and generally were smaller than littermates. Survival to weaning was reduced in carriers with 11 of the 33 dying during this period. Four mice with tail kinks at weaning had no obvious spots; in the remainder, spotting varied from a faint patch on the head to a large thoracic patch. The essential features of the phenotype are therefore tail kinks, small body size and white spots and the mutation has been given the gene symbol Tks. Weights at birth and weaning were measured in litters of matings set up to maintain the mutation. For neonates classified at birth as Tks/+ by the presence of a kinked tail, average weights were 1.38gm (SD +/- 0.18; 32 animals) compared with 1.62gm (SD +/- 0.18; 39 animals) for wild type. The respective weights of those surviving to birth were 8.04gm (SD +/- 2.73; 14 animals) and 11.96gm (SD +/- 1.46; 35 animals). To date, intercrosses of heterozygotes have not produced any apparent homozygotes. Linkage studies. A variety of linkage testing stocks were used to determine the chromosomal location of Tks; loci on chromosome 9 provided evidence of linkage and only these data are presented here. Tks/+ heterozygotes were mated to mice homozygous for dilute (d) and short ear (se); carrier F1 animals were backcrossed to the homozygous recessive stock and their offspring screened for the segregation of Tks and d se (see Table); Cross: + d se/+ d se x Tks + +/+ d se; + d se/+ d se: 13; Tks + +/+ d se: 2; + + +/+ d se: 6; Tks d se/+ d se: 0. Cross: Tks + +/+ d se x + d se/+ d se; + d se/+ d se: 39; Tks + +/+ d se: 2; + + +/+ d se: 19; Tks d se/+ d se: 2. Although Tks carriers were identified at birth in the backcrosses, few of these survived sufficiently long to be classified for the recessive marker genes. In total, 77 non-Tks/+ animals were classified: 52 were + d se/+ d se, 25 were + + +/+ d se. If Tks and the marker loci are linked, then the number of homozygous d se offspring should be greater than that of heterozygotes; the ratio of homozygotes to heterozygotes did indeed differ significantly from 1:l (x2 = 9.47, p = 0.002). Only 6 Tks/+ animals survived sufficiently long to allow classification for the marker loci, of these 4 were Tks + +/+ d se and 2 were Tks d se/+ d se. Combination of these data therefore gave 27 recombinants out of 83 animals providing an estimate of 32.5 (SE +/- 5.l)cM from Tks to d se. The location of Tks was further investigated using the Robertsonian translocation Rb(9.19)163H. F1 Tks +/ + Rbl63H animals were mated to chromosomally normal mice; their progeny were classified for Tks, and post-weaning age animals screened cytogenetically for the Robertsonian translocation. The numbers of progeny found with the following genotypes were: Tks +/ + +, 25; + +/ + Rbl63H, 35; Tks Rbl63H/ + +, 3; + +/ + +, 3. The low proportion of recombinants indicate the mutation maps proximally, and gives an estimate of 9.1 (SE +/-3.5)cM from the centromere to Tks. Discussion. Our analyses have shown that a radiation-induced mutation giving a kinked tail, small body size and variable white spotting maps proximally on chromosome 9. The breeding data from the cross using the markers d se indicate the locus is approximately 32 cM proximal to this region. This would place the new mutant about 6 cM distal to Pvs the most proximally mapped locus on chromosome 9. The data from the linkage study with Rb(9.19)163H place the locus slightly more distally, approximately 9cM from the centromere. Interestingly, Cattanach et al [2] have described an induced mutation causing reduced body size and spotting which also maps proximally on chromosome 9. Cytogenetic analysis showed this mutation to involve a small deletion of approximately 5% of chromosome 9. When mated to the proximal recessive marker gene curly whiskers (cw) heterozygous expression of the marker occurs. We have examined G-banded somatic chromosomes from Tks/+ mice (using both chromosomally normal mice and animals carrying Rb(9.19)163H to distinguish wild type and Tks-bearing chromosomes) and have found no evidence of a deletion or other chromosomal rearrangement associated with Tks. Moreover, crosses with cw/cw mice did not result in the heterozygous expression of the marker in cw +/+ Tks progeny. Thus although the mutants described by Cattanach et al [2] and here share some phenotypic features and both map proximally on chromosome 9, they are not identical. Acknowledgements. This work was supported in part by Euratom contract Bi6-143. We thank Dr BM Cattanach for his comments on the manuscript. References 1. Tease C and Fisher G. (1989) Mouse News Letter 83, 159-160. 2. Cattanach BM, Burtenshaw MD, Rasberry C, and Evans EP. Nature Genetics (in press). |
