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Dis Model Mech. 2018 Sep 27;11(9). pii: dmm035923. doi: 10.1242/dmm.035923.

The class I myosin MYO1D binds to lipid and protects against colitis.

Author information

1
Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390-8505, USA.
2
Department of Internal Medicine, Division of Gastroenterology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8505 USA.
3
Quantitative Biomedical Research Center, Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
4
Center for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390-8505, USA bruce.beutler@utsouthwestern.edu.

Abstract

Myosin ID (MYO1D) is a member of the class I myosin family. We screened 48,649 third generation (G3) germline mutant mice derived from N-ethyl-N-nitrosourea-mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). We found and validated mutations in Myo1d as a cause of increased susceptibility to DSS-induced colitis. MYO1D is produced in the intestinal epithelium, and the colitis phenotype is dependent on the nonhematopoietic compartment of the mouse. Moreover, MYO1D appears to couple cytoskeletal elements to lipid in an ATP-dependent manner. These findings demonstrate that MYO1D is needed to maintain epithelial integrity and protect against DSS-induced colitis.

KEYWORDS:

Dextran sodium sulfate; Inflammatory bowel disease; N-ethyl-N-nitrosourea

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