A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration ( Wld S ) mouse

Exons of three genes were identified within the 85-kilobase tandem triplication unit of the slow Wallerian degeneration mutant mouse, C57BL/Wld S . Ubiquitin fusion degradation protein 2 (Ufd2 ) and a previously undescribed gene,D4Cole1e , span the proximal and distal boundaries of the repeat unit, respectively. They have the same chromosomal orientation and form a chimeric gene when brought together at the boundaries between adjacent repeat units inWld S . The chimeric mRNA is abundantly expressed in the nervous system and encodes an in-frame fusion protein consisting of the N-terminal 70 amino acids ofUfd2 , the C-terminal 302 amino acids ofD4Cole1e , and an aspartic acid formed at the junction. Antisera raised against synthetic peptides detect the expected 43-kDa protein specifically inWld S brain. This expression pattern, together with the previously established role of ubiquitination in axon degeneration, makes the chimeric gene a promising candidate forWld . The third gene altered by the triplication,Rbp7 , is a novel member of the cellular retinoid-binding protein family and is highly expressed in white adipose tissue and mammary gland. The whole gene lies within the repeat unit leading to overexpression of the normal transcript inWld S mice. However, it is undetectable on Northern blots ofWld S brain and seems unlikely to be theWld gene. These data reveal both a candidate gene forWld and the potential of theWld S mutant for studies of ubiquitin and retinoid metabolism.