A novel null allele of mouse DSCAM survives to adulthood on an inbred C3H background with reduced phenotypic variability

DSCAMs are cell adhesion molecules that play several important roles in neurodevelopment. Mouse alleles of Dscam identified to date do not survive on an inbred C57BL/6 background, complicating analysis of DSCAM-dependent developmental processes because of phenotypic variability related to the segregating backgrounds needed for postnatal survival. A novel spontaneous allele of Dscam, hereafter referred to as Dscam²(J), has been identified. This allele contains a four base pair duplication in exon 19, leading to a frameshift and truncation of the open reading frame. Mice homozygous for the Dscam²(J) mutant allele survive into adulthood on the C3H/HeJ background on which the mutation was identified. Using the Dscam²(J) allele, retinal phenotypes that have variable severity on a segregating background were examined. A neurite lamination defect similar to that described in chick was discovered in mice. These results indicate that, in the retina, additional DSCAM-dependent processes can be found by analysis of mutations on different genetic backgrounds.