| First Author | Burtenshaw M | Year | 1995 |
| Journal | Mouse Genome | Volume | 93 |
| Issue | 2 | Pages | 422-3 |
| Mgi Jnum | J:35325 | Mgi Id | MGI:82775 |
| Citation | Burtenshaw M, et al. (1995) Six new radiation-induced deletions. Mouse Genome 93(2):422-3 |
| abstractText | Full text of Mouse Genome: 5. Six new radiation-induced deletions. We have reported the occurrence of a number of large cytogenetically visible deletions, formerly a rare class of mutation (Cattanach et al, Nature Genetics 3:56-61, 1993; Cattanach et al, MG 91:853-4, 1993; Cattanach et al, MG 92:111-113, 1994 and Cattanach et al 92:349-50, 1994). Here, we report a farther 6 examples, all deriving in the Fl generation following combined chemical-X- radiation exposures to spermatogonial stem cells. All subsequent crosses utilised Fl hybrid C3H/HeH x 101/H stock animals. Del (1) 58H First detected in a female, retarded at birth and weaning, and with 70% viability of mutants to weaning. Other phenotypic effects were restricted to darker than normal coat with darker skin pigmentation as visualised on ears, feet and tail. Cytogenetic analysis revealed a deletion of about 15% of Chr 1, spanning bands 1C5 - 1E2.2. Three previously identified large deletions in the central region of this chromosome, Del (1C5-E4) Dmh 6H, Del (1C/D - E4) Swf 27H and Del (1D/E - E2.3) Sdm 33H represent 28%, 22% and 15% respectively of Chr 1. Unlike Del (1) 58H, all three show some degree of abnormality of the skull, this being most marked in the largest deletion. The absence of such abnormalities in Del (1) 58H could indicate that the region 1E2.2 - 1E3 is associated with normal skull development. Del (2) 59H The original animal was a male, recognised as small at birth and weaning and showing a slightly domed, short head at weaning and adult ages. The phenotype was inherited through subsequent generations of outcrosses, breadth across the eyes being seen as an additional feature, the eyes often being small and gummy. More notable, however, was a hyper-pigmentation of the genitalia, variable in degree, but noted in a number of deletion syndromes. Despite the growth retardation, viability to birth and subsequently to weaning was not seriously impaired (about 70% in each case). Breakpoints are in 2E2 and 2E5, the deletion spanning approximately 11% of Chr 2. This deletion overlaps, and extends proximally, the region deleted in the previously described Del (2) Swt 35H (Cattanach et al MG 91:854, 1993). Perhaps somewhat surprisingly, the overall (50%) viability of the mutant Del (2) 59H is over three times higher than in the smaller deletion Del(2) Swt 35H. Del (14) 60H This mutant arose in a female showing small size and white foot and tail markings. When crossed to a normal male it produced only wild type offspring, excluding a dominant mode of inheritance, but 8 of the 17 had domed heads at 1-2 weeks of age, this feature flattening out with age. In subsequent crosses a proportion at weaning were also found to have twisted jaws with mal-occlusion of the teeth. Viability to birth was normal and only a low (20%) loss was noted after this. On crossing to recessive spotting (s), the mutation proved to be an allele at this locus, the head phenotype being the single novel characteristic. In common with all radiation-induced s alleles previously studied in these experiments, this mutation proved to be a distal Chr 14 deletion (distinguished from the others only by its head shape). Cytogenetic analysis revealed a deletion spanning bands 14 E2.2-2.4 (17% of Chr14). Del (3) 61H This mutation was detected in a male and was retained for testing only on the basis of its small size at birth and notable growth retardation at weaning. These characteristics were inherited, but an additional feature commonly noted was the indication of a minor cleft down the centre of the muzzle and nose, the latter being unpigmented and shortened. The eyes also often appeared small and gummy. Viability even to birth appeared to be greatly impaired as only 7 mutants were detected among 116 offspring from the original male, and only 11 from two daughters among their 75 young. This, together with the subsequent recovery rate at weaning suggested that the head anomaly represented a mild form of a more deleterious mutant phenotype. This has not been verified as yet, however. The original male exceptionally gave highly variable litter sizes, several litters comprising only 1 or 2 young while others were as large as 11. One son, set up in a mating, proved virtually sterile, producing only a single litter and thereafter failing to get any of a series of females pregnant. Openings on females mated to two further sons demonstrated only rare implants, suggesting oligospermia was the cause of the infertility. Two daughters of the original male, however, proved fully fertile with a mean litter size of 6.8. Chromosomal analysis of the original male revealed a deletion of Chr 3, involving bands 3D-El or 3E1-E2 (in either case representing 8.5% of the chromosome). Four separate examples of deletions in this region of Chr 3 have previously been shown to be associated with male subfertility (Burtenshaw et al, MG 92:349-350, 1994) and this finding of a fifth, confirms the conclusion that the segment must carry a factor necessary in a diploid dose for successful spermatogenesis to take place. |
