title: Molecular characterization of the mouse In(10)17Rk inversion and identification of a novel muscle-specific gene at the proximal breakpoint.
abstract: Chromosomal rearrangements provide an important resource for molecular characterization of mutations in the mouse. In(10)17Rk mice contain a paracentric inversion of approximately 50 Mb on chromosome 10. Homozygous In(10)17Rk mice exhibit a pygmy phenotype, suggesting that the distal inversion breakpoint is within the pygmy locus. The pygmy mutation, originally isolated in 1944, is an autosomal recessive trait causing a dwarf phenotype in homozygous mice and has been mapped to the distal region of chromosome 10. The pygmy phenotype has subsequently been shown to result from disruption of the Hmgi-c gene. To identify the In(10)17Rk distal inversion breakpoint, In(10)17Rk DNA was subjected to RFLP analysis with single copy sequences derived from the wild-type pygmy locus. This analysis localized the In(10)17Rk distal inversion breakpoint to intron 3 of Hmgi-c and further study determined that a fusion transcript between novel 5' sequence and exons 4 and 5 of Hmgi-c is created. We employed 5' RACE to isolate the 5' end of the fusion transcript and this sequence was localized to the proximal end of chromosome 10 between markers Cni-rs2 and Mtap7. Northern blot analysis of individual tissues of wild-type mice determined that the gene at the In(10)17Rk proximal inversion breakpoint is a novel muscle-specific gene and its disruption does not lead to a readily observable phenotype.
authors.affiliation: Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA. kfbenson@u.washington.edu
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Benson
authors.forename: Kiran
authors.initials: K
authors.lastname: Chada
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D019677:Artificial Gene Fusion; D001483:Base Sequence; D015139:Blotting, Southern; D019457:Chromosome Breakage; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D018076:DNA, Complementary; D010450:Endopeptidases; D005796:Genes; D025743:HMGA2 Protein / Q000235:genetics; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D014018:Tissue Distribution
chemical_list: D018076:DNA, Complementary; D025743:HMGA2 Protein; D009124:Muscle Proteins; D010450:Endopeptidases; C095298:prenylated peptide-specific endoprotease