THE LIDGAP-GATES (LG(GA)) MUTATION FOR OPEN EYELIDS AT BIRTH MAPS TO MOUSE CHROMOSOME-13

Complex nonadditive interactions between specific alleles at multiple loci may underlie many so-called multifactorial threshold birth defect s. The open-eyelids-at-birth defect in mice is a good model for these defects, and an understanding of its genetic complexity begins with ma pping the participating loci. The open-eyelids defect can be part of a syndrome or can occur with no other obvious phenotypic effects. Of th e latter nonsyndromic forms, the lidgap series includes four extant mu tations that are considered to be alleles based on complementation tes ts. All show genetic complexity in segregation ratios. None has been m apped previously. On the basis of a strategy of mapping the mutation w ith the simplest inheritance pattern first, we generated an extensive exclusion map for lidgap-Gates, lg(Ga), using morphological and protei n polymorphisms. We then screened the non-excluded regions in a congen ic strain, AEJ.LGG-lg(Ga), for SSLP markers and located the differenti al chromosome segment containing the lg(Ga) locus in a region near the distal end of mouse Chromosome (Chr) 13. This linkage was confirmed a nd refined by typing SSLPs in 64 F-2 and 74 BC1 progeny of a cross of LGG/Bc (lg(Ga)\ lg(Ga)) to SWV/Bc. The lg(Ga) mutation maps to a 1- to 2-cM region between D13Mit76 and D13Mit53. Integrin alpha 1 and integ rin alpha 2, which map to the same general region, are possible candid ate loci, based on their embryonic expression and cellular function. E vidence is also presented for a common unlinked recessive suppressor o f the open eyelids trait caused by lg(Ga).