International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


POSTER 162 - ANALYSIS OF A NEW DOMINANT HAIRLOSS MUTANT MAPPING TO MOUSE CHROMOSOME 11.

Weber JS1, Rahajeng J1, Kovar J2

1 University of Nebraska, Lincoln, United States, 2 LI-COR BioSciences, Lincoln, United States

Development and maintenance of hair in mammals requires multiple genes that control position, growth cycle, and type of hair. Since most of the genes regulating hair have not been determined, we took a genetics-based approach to identify genes involved in hair formation. An ENU mutagenesis project was initiated to screen mice for a variety of abnormalities including hair problems. Mutagenized C57BL/6 males were bred to produce dominant and recessive mutants. A new dominant mutant was found which exhibited hair loss starting between 14 and 21 days of age.  Affected animals undergo progressive rounds of hair loss ending with hair only around the snout, legs and base of the tail.  To map the Hairloss gene, affected mice were outcrossed to DBA/2J mice to produce F1s. F2 mice were generated by backcrossing affected F1 mice to DBA/2J mice. DNA from 50 Hairloss and 50 wild-type F2 mice were pooled by phenotype and amplified with 103 microsatellite markers equally spaced across the genome and polymorphic for C57BL/6 and DBA/2J alleles. Hairloss was mapped initially from 213 F2 mice to distal mouse Chromosome 11 between D11Mit39 and D11Mit181. Individual genotyping identified 35 recombinants between the linked markers. A tiered-mapping approach was used to narrow down the non-recombinant region to approximately 1.77Mb, the size of the region between new markers D11NEB2 (98.3Mb) and D11NEB1 (100.07Mb). Three mice have recombination breakpoints between D11NEB1 and Hairloss; one mouse has a recombination breakpoint between D11NEB2 and the mutant gene. No new recombinants have been found between D11NEB1 and D11NEB2 after genotyping an additional 144 F2 mice. We have found candidate genes in the nonrecombinant region, including homologs of Gasdermin.  We will present analysis of these loci along with more detailed studies of the hair phenotype. 

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