| First Author | Compton | Year | 1990 |
| Journal | Mouse Genome | Volume | 86 |
| Pages | 240 | Mgi Jnum | J:16020 |
| Mgi Id | MGI:64115 | Citation | Compton, et al. (1990) Defective development of embryonic ectoderm of velvet coat mice is associated with deletion of type II keratin genes. Mouse Genome 86:240 |
| abstractText | Full text of Mouse Genome contribution: 9. Defective development of embryonic ectoderm of velvet coat mice is associated with deletion of type II keratin genes. We have identified a keratin gene deletion associated with the mutation velvet coat (Ve). Embryos homozygous for Ve degenerate in utero at 5-8 days due to a deficiency in embryonic ectoderm development, while heterozygous Ve/+ mice display mildly abnormal hair texture and normal fertility. Heterozygous Ve mice Ve/+) were mated in an interspecies cross with M. spretus mice (+/+) and DNA from all backcross progeny were analyzed with a keratin Kl gene probe. Non-Ve DNA contained both keratin alleles, whereas the DNA from mice carrying one wild-type Chr 15 and one Ve-Chr 15 was found to contain only a single keratin allele corresponding to that of the wild-type parent. The intensity of hybridization to DNA from heterozygous Ve mice was consistent with a hemizygous K1 genotype. Similar analysis performed with specific gene probes for K4, K5, K6 and hair keratin Bl indicates these genes are also deleted, and confirms they are part of the Krt-2 locus of type II genes on mouse Chr 15. Most interestingly, the entire Krt-2 locus is not deleted in Ve, since the type II gene K8 was found not to be deleted. We conclude that one end of the Ve-associated deletion lies in the Krt-2 locus. The deletion does not encompass other genes known to be closely-linked to Krt-2, the genes for homeobox-3.1 (Hox-3.1), glycerol phosphate dehydrogenase 1 (Gdc-I), mouse mammary tumor virus integration site 1 (Int-1) and the trans-acting gene regulator Spl. The Ve mutation is tightly linked to two other epidermally-acting mutations, Ca (caracul, affecting hair morphology) and Sha (shaven, affecting hair shaft and follicle development), and to mk (microcytic anemia), sw (swaying) and med (motor-end plate disease). Phenotypic complementation analysis indicates neither mk, nor med, are deleted in Ve, but the gene affected by the Sha mutation is probably within the Ve- associated deletion since Sha/Ve mice display hairloss phenotypically identical to Sha/Sha mice. Since the Ve mutation arose in an X-irradiation experiment it is very likely that this deletion accounts for abnormal embryonic and epidermal development in Ve mice. Abnormal keratin expression is a candidate for the earliest molecular defect in Ve/Ve embryogenesis. Keratin K8 is the only type II keratin reported to be expressed up to 8-9 days in mouse embryos. We tested whether grossly abnormal keratin K8 expression could be detected in embryos from Ve/+ x Ve/+ matings by immunohistochemistry. Keratin K8 positive staining in extraembryonic and endodermal tissues of normal and putative Ve/Ve 5.5 day and 7.5 day embryos was indistinguishable. To identify the primary molecular defect in Ve/Ve embryogenesis, further examination of type I1 keratin expression during early mouse embryogenesis, and determination of the molecular structure of the Ve deletion is being pursued. (Compton, F.H. Ruddle [Yale University], D.M. Ferrara) |
