title: SM2(+/-) male mice are predisposed to develop urinary tract obstruction and hyper contractility of the bladder smooth muscle upon ageing.
abstract: We previously showed that complete loss of smooth muscle myosin heavy chain isoform 2 (SM2) resulted in postnatal lethality, but in het mice a partial loss of SM2 (SM2(+/-)) was accompanied by down-regulation of SM1 with unaltered SM2:SM1 ratio. To determine whether a normal bladder function would be maintained throughout its lifespan, we aged WT and SM2(+/-) mice up to 18 months and analyzed a) SM2:SM1 ratio b) bladder smooth muscle structure and c) function in SM2(+/-) het mice. A notable finding was that ~50% of 15-18 months old male SM2(+/-) mice exhibited urinary retention in bladder with the distention of upper urethra. In SM2(+/-) mouse bladder with urinary retention, the SM2:SM1 ratio was decreased but not in SM2(+/-) mouse bladder that did not develop urinary retention. Interestingly in the distended bladder the expression levels of α-actin and tropomyosin remained unaltered despite a reduction in the number of myosin thick filaments. These distended bladders showed hypersensitivity to submaximal K(+) depolarization and M3-receptor stimulation, without a significant increase in myosin light chain phosphorylation. We therefore suggest that a partial loss of SM2 may predispose male mice to develop lower urinary tract obstruction during ageing. In addition our data suggest that bladder obstruction can cause a further reduction in SM2 expression and SM2:SM1 ratio, and a hyper-contractility of the bladder smooth muscle.
authors: Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, USA.
authors: Mei
authors: M
authors: Chi
authors: Yingbi
authors: Y
authors: Zhou
authors: Danesh
authors: D
authors: Sopariwala
authors: Muthu
authors: M
authors: Periasamy
mesh_terms: D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D051379:Mice; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics; D043587:Receptor, Muscarinic M3 / Q000235:genetics / Q000378:metabolism; D014335:Tropomyosin / Q000096:biosynthesis / Q000235:genetics; D014517:Ureteral Obstruction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016055:Urinary Retention / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D000199:Actins; D018994:Myosin Light Chains; D043587:Receptor, Muscarinic M3; D014335:Tropomyosin; D018995:Myosin Heavy Chains