401. Physical mapping of the Tec and Gabrb1 loci reveals that the Wsh mutation on mouse chromosome 5 is associated with an inversion.
- Author
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Nagle DL, Kozak CA, Mano H, Chapman VM, and Bućan M
- Subjects
- Animals, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Pigmentation genetics, Chromosome Inversion, Mutation, Protein-Tyrosine Kinases genetics, Receptors, GABA genetics, Restriction Mapping
- Abstract
In the mouse, mutations in the c-Kit proto-oncogene, a member of the receptor tyrosine kinase (RTK) gene family, have pleiotropic effects on hematopoiesis, pigmentation and fertility (dominant spotting, W). However, in the Wsh allele the defect is confined to abnormal pigmentation caused by the disruption of 5' regulatory sequences of Kit leaving an intact structural gene. In this report, the previously published physical map around the Pdgfra-Kit-Flk1 RTK loci is extended by mapping the loci encoding the GABAA (gamma-aminobutyric acid) receptor subunit beta 1, Gabrb1 and a cytoplasmic kinase (Tec) 3 Mb proximal to Kit. PFGE analysis of the wild-type (C57BL/6J) chromosome demonstrates the following gene order: cen-Gabrb1-Tec-Pdgfra-Kit, whereas the analysis of Wsh/Wsh DNA is consistent with the order: cen-Gabrb1-Pdgfra-Tec-Kit. This altered physical map can be explained by an inversion on the Wsh chromosome located proximally to the Kit locus and spanning the 2.8 Mb Pdgfra-Tec chromosomal segment. This high resolution physical mapping study identifies large DNA fragments that span the two inversion breakpoints and potentially carry Kit upstream regulatory elements involved in the control of Kit expression during embryonic development.
- Published
- 1995
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