Mapping of Zyx coding for zyxin in the rat and its exclusion as a candidate gene for lymphopenia.

Abstract

Zyxin is a phosphoprotein localized at sites of cell adhesion. It binds to the guanine nucleotide exchange factor Vav1 involved in thymocyte selection and is possibly involved in the Vav1 dependent pathway of TCR signaling (Hobert et al., 1996). This makes the zyxin gene (Zyx) a putative candidate for the rat diabetes susceptibility gene, Iddm1, also known as Lyp. A mutation in the latter gene is responsible for a profound T cell lymphopenia that resembles the lymphopenia of Vav1KO mice. In addition, the human zyxin-gene is located very close to a number of genes mapping in the vicinity of Iddm1 in the rat (Zumbrunn and Trueb, 1998). We therefore proposed Zyx as a positional candidate for rat Iddm1. In this study we have mapped Zyx with a rat radiation hybrid (RH) panel using mouse-derived primers for PCR amplification and detection of a Single-Strand Conformational Polymorphism between hamster and rat. The amplified rat segment was 95% identical to mouse Zyx. We positioned Zyx to rat chromosome 4 between markers Prss1 and D4Mit5. Since Iddm1 is positioned between markers D4Rat75 and Npy this excludes Zyx as a candidate gene for Iddm1. Materials and methods