RNA-seq of isolated pancreatic islets from beta-cell-specific Jazf1 knock-out mice

Genome-wide association studies (GWAS) have identified several susceptibility loci for T2D. Among these loci, juxtaposed with another zinc finger protein 1 gene (JAZF1) has been shown as one of the top candidates associated with T2D development. JAZF1 gene encodes a protein containing three putative zinc-finger motifs and is expressed in a variety of tissues in mice and humans. However, the biological function of JAZF1 remains largely unknown, although its effect on pancreatic beta cells has not been investigated. To study the physiological function of JAZF1 in pancreatic islets, we generated conditional beta-cell-specific Jazf1 knock-out mice by crossing Jazf1fl/fl mice with a floxed exon 3 with RIP-Cre transgenic mice that express Cre-recombinase under the control of the rat insulin 2 promoter. We isolated islets from 8 weeks-old RIP-Cre Jazf1fl/fl male mice and their littermates controls Jazf1 fl/fl that were fed a chow diet.

全基因组关联研究（Genome-wide association studies, GWAS）已成功鉴定出多个与2型糖尿病（Type 2 Diabetes, T2D）相关的易感基因座。在上述基因座中，邻位锌指蛋白1基因（JAZF1）被证实为与T2D发病进程密切相关的核心候选基因之一。JAZF1基因编码一种含有三个推定锌指结构域的蛋白质，在小鼠与人类的多种组织中均有表达。然而，尽管目前尚未有针对其对胰岛β细胞（pancreatic beta cells）作用的相关研究，JAZF1的具体生物学功能仍未被充分阐明。为探究JAZF1在胰岛中的生理功能，我们通过将携带floxed第3外显子的Jazf1fl/fl小鼠与大鼠胰岛素2启动子（rat insulin 2 promoter）驱动Cre重组酶表达的RIP-Cre转基因小鼠（RIP-Cre transgenic mice）交配，成功构建了β细胞特异性条件性Jazf1敲除小鼠模型。我们从饲喂普通饲料（chow diet）的8周龄雄性RIP-Cre Jazf1fl/fl小鼠及其同窝Jazf1fl/fl对照小鼠中分离得到了胰岛组织。