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Mapping gaping lids : a mutation causing open eyelids at birth in mouse

University of British Columbia

Gaping lids (gp) is an autosomal recessive mutation that arose spontaneously in the C57BL/6-ax strain of mice and is now maintained in the inbred strain GP/Bc. The purpose of this study included the mapping of the gp mutation, analysis of its segregation after two outcrosses to normal (non-open eyelid) strains and characterization of the mutant phenotype. The main objective, to map the gp locus, was undertaken based on the hypothesis that the loci with mutations that cause open eyelids with simple Mendelian transmission patterns may also be loci involved in the open eyelids traits with more complex inheritance. Since these mutations are viable, they are good models for studying the interaction of multiple loci in a genetically complex birth defect. The gaping lids mutation was mapped close to the centromere at the proximal end of chromosome 11, employing PCR amplification of informative SSLP marker loci, initially using 41 gaping lids F2 progeny from a cross of GP/Bc to the normal strain CBA/J, followed by a refinement of the region using 23 gaping lids F2 progeny from a second outcross of GP/Bc to ICR/Be, another normal inbred strain. Based on the recombination breakpoints, gp is within 10 cM of D l lMit80 and 2 cM o f DllMit71. The epidermal growth factor receptor gene (Egfr) was also mapped to mid-chromosome 11 between DllMit226 and DllMitl51 , employing PCR amplification of SSLP markers, using mice carrying a null allele at this locus. This map location supports the finding that gp and Egfr are not allelic as determined by a complementation test between Egfr⁺/⁻ and GP/Bc. gp showed reduced penetrance, 82% and 33% in the outcrosses to CBA / J and ICR/Be, respectively, but it was determined that this was likely due to suppressors-of open eyelids loci introduced by the normal strains and not prenatal death of gp/gp progeny. The only phenotypic anomaly associated with this mutation appears to be eyelids at birth, due to failure of normal eyelid closure during late gestation.

Thesis/Dissertation

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2009-07-06

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http://hdl.handle.net/2429/10242

Medical Genetics

University of British Columbia

UBCV

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