The disabled 1 gene is disrupted by a replacement with L1 fragment in yotari mice

Abstract

The yotari autosomal recessive mutant mouse has a phenotype that is almost identical to that of the reeler mouse. We reported in our previous study that the yotari mouse expresses a mutated form of disabled 1 ( Dab1) mRNA resulting in no Dab1 protein. In this study, we demonstrate that the yotari mutation is caused by a replacement of gene sequence with a long interspersed nuclear element (L1) fragment. The nucleotides of two complete exons and part of an additional exon of Dab1 were eliminated as well as three introns by this substitution. The substituted L1 fragment contains 962 nucleotides and is highly homologous to the members of the T F subfamily of L1. It is truncated at both the 5′ and 3′ ends and contains two blocks in a head-to-head arrangement. Based on the DNA sequences around the replacement we developed a screening method that enables us to distinguish wild type, yotari, and heterozygous mice. This method should greatly contribute to analyses of the early anatomical and physiological consequences of the yotari mutation.