| First Author | Rasberry C | Year | 1993 |
| Journal | Mouse Genome | Volume | 91 |
| Issue | 4 | Pages | 851-53 |
| Mgi Jnum | J:16303 | Mgi Id | MGI:64387 |
| Citation | Rasberry C, et al. (1993) Three new mottled mutations - Mo10H, Mo11H, and Mo12H. Mouse Genome 91(4):851-53 |
| abstractText | Full text of Mouse Genome contribution: Research News: 1. Three new mottled mutations. Three new mutations showing variegated grey-agouti phenotypes resembling those of mottled (Mo) alleles have been detected in recent radiation mutagenesis studies. On the basis of their inheritance and results of linkage tests with tabby (Ta) they have been deduced to be mutations at the Mo locus. Accordingly they have been given the gene symbols, Mo10H, Mo11H and Mo12H in order of recovery. Mo10H. Mo10H arose in a specific locus experiment in which F1 hybrid (C3H/HeH x 101/H) males received a combined chemical - X-ray treatment of 2.0 mg/kg TEM plus 6 Gy X-rays (24h interval) and were mated to PT tester stock females after their return to fertility. The mutation is therefore likely to have derived from spermatogonial irradiation. The original mutant females and most of her heterozygous descendants exhibited a lower level of grey patching than typically found with Mo alleles. In addition, the vibrissae were commonly straight at birth, rather than waved. The hemizygous males, on the other hand, could reliably be detected at birth by their wavy vibrissae and at later ages showed a near-white coat almost devoid of all pigment. As soon as capable of walking these males showed an uncoordinated gait. This became progressively worse such that about 14-17 days there appeared to be a total loss of limb control. Survival beyond 17 days was zero. Based on classifications at 1-2 weeks of age, there was a shortage of both heterozygous females and hemizygous males from crosses of Mo10H+ females with wild type males (147 Mo10H+ females, 206 + females, 95 Mo10HY males, 206 + Y males). The litter size (7.3) compared favourably with that of F1 hybrid females (~ 8.3) and this suggests that pre-natal loss of either class may be modest. Post-natal loss can readily account for the shortage of males in view of their phenotypic effects. Poor penetrance may best explain the shortage of females, but no test matings to confirm this conclusion have yet been made. Repulsion linkage tests with Ta produced the following classes of young, males being identified at birth and females at weaning. 19 Mo10H+ females, 33 Ta+ females, 2 Mo10H Ta/+ + females, 0 + females, 31 Mo10H Y males, 27 TaY males, 0 Mo10H Ta/Y males and 1 +Y male, total 113. In view of the poor penetrance of the mutant in females the RF can best be estimated in males. On this basis, the frequency is 1.64 +/- 1.63, a figure reasonably consistent with the Mo - Ta consensus map distance of 4 cM (Lyon and Kirby, MG 91:78, 1993). Compounds of Mo10H with Moblo displayed a near uniform grey-white coat and appeared fully viable. Five such Mo10H/Moblo females were mated and proved fertile. Only 15 young were reared and all showed a Mo phenotype. Mo11H. This mutant arose in a similar specific locus study in which the treated males received two doses of 500 mg/kg hydroxyurea 3 hours apart, followed by a 6 Gy X-ray exposure 24h later. As with Mo10H, the mutation is likely to have derived from spermatogonial irradiation. Mo11H heterozygotes showed a more extreme expression than M10H, the coat being more extensively and obviously variegated. Few hemizygous males have been recorded; those found resembled Mo10H Y males in all respects. Crosses of Mo11H+ females with wild-type males produced young of the following classes: 118 Mo11H+ females, 206+ females, 3 Mo11H Y males and 179+Y males. At birth, the sex ratio was skewed in favour of females (386 females:200 males). This observation together with a rather low litter size (6.07) suggests that most Mo11H Y males die pre-natally. Losses of females between birth and weaning were about twice as high as among males. Post-natal loss is therefore likely to be the major cause of the shortage of Mo11H females at weaning. Repulsion linkage tests with Ta produced the following classes of young: 12 Mo11H+ females, 45 Ta+ females, 4 Mo11H Ta/++ females, 4 + females, 0 Mo11H Y males, 48 TaY males, 0 Mo11H Ta/Y males and 1 +Y male, total 114. Based on the non- recombinant Ta and recombinant + class, the RF can be estimated to be 5.10 +/- 2.22, consistent with the map position of Mo. Mo12H. This mutation arose, like Mo10H and Mo11H in a specific locus experiment in which wild type males had been exposed to X-rays. However, unusually, the original mutant was a variegated male who was fertile and produced some mutant daughters. As the male must have received his Y from his father, the X carrying the mutation must have derived from his PT tester stock mother; the mutation must therefore have been of spontaneous origin. His variegated phenotype and ability to transmit the mutation to a proportion of his female progeny (6 out of 47) indicates that he was a gonosomic mosaic, the mutation occurring after fertilisation and prior to the separation of the somatic and germ lines of the embryo. The Modp allele also arose by this means (Phillips, Genet. Res. 2:290-295, 1961). The Mo12H heterozygotes typically showed an extreme variegated phenotype, a majority of the coat being near-white. The whiskers were also noticeably curly at birth. The more extreme heterozygotes often showed a progressive deterioration of mobility and balance. Skeletal effects, notably affecting the limbs and toes were commonly found, and most Mo12H+ females were smaller than their + sibs. Viability to weaning was substantially reduced (65%). No hemizygous males have been detected. Litters from Mo12H+ females were smaller than normal (5.1) and showed a skewed sex ratio (191 females : 105 males). Both of these observations are consistent with a pre-natal loss of hemizygous Mo12H males. Based on classifications at birth, crosses of Mo12H+ females with + males produced 56 Mo12H+ females, 88 + females, 0 Mo12H Y males and 76 +Y males. Some pre-natal loss of females was therefore suggested, although this was not evident in linkage tests. Repulsion linkage tests with Ta produced 33 Mo12H+ females, 33 Ta+ females, 2 Mo12H Ta/+ + females, 5 + females, 0 Mo12H Y males, 58 TaY males, 0 Mo12H Ta/Y and 0 +Y males, total 131. Using only the non-recombinant Ta and recombinant + classes, the RF can be estimated to be 5.21 +/- 2.27. (Rasberry and Cattanach). (This work was supported in part by Euratom Contract F13P-CT920055). |
