LTW4 PROTEIN ON MOUSE CHROMOSOME-1 IS A MEMBER OF A FAMILY OF ANTIOXIDANT PROTEINS

Based on its map position, polymorphism pattern, and expression in the kidney, the gene encoding liver 20,000-30,000 MW protein 4 (LTW4) can be considered a potential candidate for the Jckm2 modifying. locus, w hich mediates the severity of polycystic kidney disease in the juvenil e cystic kidney mouse, Using two-dimensional gel electrophoresis, we i dentified variants of a 26-kDa polypeptide that differed in their isoe lectric points between the C57BL/6J anti the DBA/2J inbred strains in a pattern similar to that originally described for LTW4 protein, N-ter minal amino acid sequence was obtained by microsequencing analysis, an d full-length clones were obtained by RT-PCR amplification and charact erized. The map position of the cloned gene was determined and corresp onded to that previously described for Ltw4. The gene has homology to a class of proteins characterized as thiol-specific antioxidants that are protective against damage caused by oxidative stress. The murine M ER5 gene is also a member of this gene family and has recently been re named Antioxidant protein 1 (Aop1), based on its functional characteri zation, We therefore propose that the gene encoding LTW4 be called Aop 2. (C) 1997 Academic Press.