PUBLICATION
Loss-of-Function of CLMP Is Associated With Congenital Short Bowel Syndrome and Impaired Intestinal Development
- Authors
- Chen, S., Xu, J., Xiao, Y., Cai, H., Zhou, J., Cai, W., Wang, Y.
- ID
- ZDB-PUB-250109-172
- Date
- 2025
- Source
- Clinical genetics : (Journal)
- Registered Authors
- Keywords
- CLMP, congenital short bowel syndrome, pathogenic mechanism, smooth muscle
- MeSH Terms
-
- Coxsackie and Adenovirus Receptor-Like Membrane Protein*/genetics
- Coxsackie and Adenovirus Receptor-Like Membrane Protein*/metabolism
- Male
- Genetic Predisposition to Disease
- Humans
- Short Bowel Syndrome*/genetics
- Short Bowel Syndrome*/physiopathology
- Exome Sequencing*
- Child, Preschool
- Loss of Function Mutation/genetics
- Animals
- Female
- Gastrointestinal Motility/genetics
- Disease Models, Animal
- Receptors, Enterotoxin
- Intestines/pathology
- Mutation
- Child
- Zebrafish*/genetics
- PubMed
- 39763071 Full text @ Clin. Genet.
Citation
Chen, S., Xu, J., Xiao, Y., Cai, H., Zhou, J., Cai, W., Wang, Y. (2025) Loss-of-Function of CLMP Is Associated With Congenital Short Bowel Syndrome and Impaired Intestinal Development. Clinical genetics. :.
Abstract
Coxsackie and adenovirus receptor-like membrane protein (CLMP) mutation is identified as a genetic risk factor of congenital short bowel syndrome (CSBS). However, the specific pathogenic mechanism remains unclear. This study aimed to explore the clinical manifestations, genetic characteristics, and molecular mechanisms underlying CSBS caused by CLMP mutations. Whole-exome sequencing was performed to determine the pathogenic gene mutations in children with CSBS and their family members. In addition, a zebrafish model was established by microinjecting morpholinos into zebrafish embryos to investigate the role of clmp in intestinal embryonic development. This was investigated by measuring the length of zebrafish, evaluating gastrointestinal motility, and performing qRT-PCR assays. Two children with CSBS had CLMP mutations, one with a c.244C>T (p.R82*) mutation and exons 3-5 deletion, and the other with a c.23T>A (p.L8*) mutation and exons 3-5 deletion. After knocking down clmp expression in zebrafish embryos, the intestinal length and the gastrointestinal motility decreased. Furthermore, the expression of smooth muscle-associated genes decreased significantly. Additionally, clmp mRNA partially rescued zebrafish defects caused by clmp morpholino knockdown. Clmp knockdown decreased intestinal transport dynamics and expression of smooth muscle-related genes in zebrafish. CLMP is expected to be a potential gene therapeutic target for CSBS.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping