The Mouse Homolog of the Wiskott–Aldrich Syndrome Protein (WASP) Gene Is Highly Conserved and Maps near the Scurfy (sf) Mutation on the X Chromosome

Abstract

The mouse WASP gene, the homolog of the gene mutated in Wiskott–Aldrich syndrome, has been isolated and sequenced. The predicted amino acid sequence is 86% identical to the human WASP sequence. A distinct feature of the mouse gene is an expanded polymorphic GGA trinucleotide repeat that codes for polyglycine and varies from 15 to 17 triplets in differentMus musculusstrains. The genomic structure of the mouse gene closely resembles the human with respect to exon–∞tron positions and intron lengths. The mouse WASP gene is expressed as an ∼2.4-kb mRNA in thymus and spleen. Chromosomal mapping in an interspecificM. musculus/M. spretusbackcross placed theWasplocus near the centromere of the mouse X chromosome, inseparable fromGata1, Tcfe3,andscurfy(sf). This localization makesWaspa candidate for involvement inscurfy,a T cell-mediated fatal lymphoreticular disease of mice that has previously been proposed as a mouse homolog of Wiskott–Aldrich syndrome. Northern analysis ofsftissue samples indicated the presence of WASP mRNA in liver and skin, presumably as a consequence of lymphocytic infiltration, but no abnormalities in the amount or size of mRNA present.