Smooth muscle cell (SMC)-Specific SNRK deletion in mouse causes congenital short bowel syndrome and premature death

Congenital short bowel syndrome (CSBS), a rare gastrointestinal disorder characterized by reduced small intestine length, remains etiologically undefined. This study investigates the role of sucrose nonfermenting 1-related kinase (SNRK) in intestinal smooth muscle cells (SMCs) during development and in adult homeostasis using two mouse models: a congenital SMC-specific Snrk knockout (SNRK-SMKO) and an inducible adult knockout. SNRK-SMKO mice died prematurely and exhibited shortened intestines, dilated lumens, and a thinner circular muscle layer without evidence of increased apoptosis. In contrast, adult-onset Snrk deletion had no apparent effect. Western blot analysis revealed elevated SMC contractile proteins in neonatal (postnatal day 3.5) SNRK-SMKO colons, which declined during maturation. 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assays showed persistently reduced SMC proliferation in the circular muscle layer of both small intestine and colon across postnatal developmental stages. These results establish SNRK as a critical regulator of intestinal SMC proliferation during development, with its deficiency underlies CSBS-like pathology.