Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contractility and results in postnatal death in mice
Year: 2008
Type: preprint
Abstract: The smooth muscle myosin heavy chains (SMHC) are motor proteins powering smooth muscle contraction. Alternate splicing of SHMC gene at the C-terminus produces SM1, and SM2 myosin isoforms; SM2 (200 kDa) contains a unique 9-amino-acid sequence at the carboxyl terminus, whereas SM1 (204 kDa) has a 43 amino acid non-helical tail region. To date the functional difference between C-terminal isoforms has not been established; therefore, we used an exon-specific gene targeting strategy and generated a mouse model specifically deficient in SM2. Deletion of exon-41 of the SMHC gene resulted in a complete loss of SM2 in homozygous (SM2^-/-^) mice, accompanied by a concomitant down-regulation of SM1 in bladders. While heterozygous (SM2^+/-^) mice appeared normal and fertile, SM2^-/-^ mice died within 30 days after birth. The peri-mortal SM2^-/-^ mice showed reduced body weight, distention of the bladder and alimentary tract, and end-stage hydronephrosis. Interestingly, strips from SM2^-/-^ bladders showed increased contraction to K^+^ depolarization or M3 receptor activation. These results suggest that SM2 myosin has a distinct functional role in smooth muscle, and the deficiency of SM2 increases smooth muscle contractility, and causes dysfunctions of smooth muscle organs, including the bladder that leads to the end-stage hydronephrosis and postnatal death.
Source: Nature Precedings
Authors: Mei Chi, Yingbi Zhou, Srikanth Vedamoorthyrao, Gopal Babu, Muthu Periasamy
Institution: The Ohio State University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W36097125