Seymour R E, Hasham M G, Cox G A, Shultz L D, Hogenesch H, Roopenian D C, Sundberg J P
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Genes Immun. 2007 Jul;8(5):416-21. doi: 10.1038/sj.gene.6364403. Epub 2007 May 31.
Homologues of the SHARPIN (SHANK-associated RH domain-interacting protein) gene have been identified in the human, rat and mouse genomes. SHARPIN and its homologues are expressed in many tissues. SHARPIN protein forms homodimers and associates with SHANK in the post-synaptic density of excitatory neurotransmitters in the brain. SHARPIN is hypothesized to have roles in the crosslinking of SHANK proteins and in enteric nervous system function. We demonstrate that two independently arising spontaneous mutations in the mouse Sharpin gene, cpdm and cpdm(Dem), cause a chronic proliferative dermatitis phenotype, which is characterized histologically by severe inflammation, eosinophilic dermatitis and defects in secondary lymphoid organ development. These are the first examples of disease-causing mutations in the Sharpin gene and demonstrate the importance of SHARPIN protein in normal immune development and control of inflammation.
在人类、大鼠和小鼠基因组中已鉴定出SHARPIN（与SHANK相关的RH结构域相互作用蛋白）基因的同源物。SHARPIN及其同源物在许多组织中表达。SHARPIN蛋白形成同二聚体，并在大脑中兴奋性神经递质的突触后致密物中与SHANK结合。据推测，SHARPIN在SHANK蛋白的交联和肠神经系统功能中发挥作用。我们证明，小鼠Sharpin基因中两个独立出现的自发突变cpdm和cpdm(Dem)会导致慢性增殖性皮炎表型，其组织学特征为严重炎症、嗜酸性皮炎和次级淋巴器官发育缺陷。这些是Sharpin基因致病突变的首个实例，并证明了SHARPIN蛋白在正常免疫发育和炎症控制中的重要性。
