Isolation and characterization of the mouse cystatin B gene.

Abstract

The cystatins make up a large superfamily of proteins that inhibit cysteine proteases. Recently, we showed that loss-of-function mutations in the human cystatin B gene are responsible for progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1). However, despite the known role of cystatin B in cysteine protease inhibition, it is not clear why decreased levels of this protein cause EPM1. To provide new insights into the biochemical and pathological mechanisms of EPM1, we are working toward developing an animal model for this disease. Here we present the mouse cystatin B nucleotide and amino acid sequence. We show that the mouse gene spans a 3-kb genomic region and contains 3 exons and 2 introns, identical to the structure of both the rat and human cystatin B genes. The amino acid sequence identity of the protein is 86%, 79%, and 71% to that of the rat, human, and bovine cystatin B proteins, respectively. In addition, we show that the mouse cystatin B gene is expressed in many tissues, similar to results observed previously in humans. Finally, we report the mapping of the mouse cystatin B gene (Stfb) to chromosome 10, further extending the synteny between this region of the mouse chromosome and human chromosome 21q22.3.