Analysis of cave-in-3/nNOS w-null mice

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591281
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kawasaki Medical School
• Principal Investigator: SUNADA YOSHIHIDE 川崎医科大学, 医学部, 教授 (00240713)
• Co-Investigator(Kenkyū-buntansha): MURAKAMI Tatsufumi 川崎医科大学, 医学部, 准教授 (30330591) ; OHSAWA Yutaka 川崎医科大学, 医学部, 講師 (80246531)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 筋ジストロフィー / 再生医療 / シグナル伝達 / 国際情報交換

Outline of Final Research Achievements

Caveolin, an intergal membrane protein of the plasma membrane caveolae, binds to and regulates nitric oxide synthases (NOS) in several cells and tissues. However, interaction of caveolin-3 and neuronal NOS (nNOS) in myofiber has remained unknown. We previously generated a model of limb-girdle muscular dystrophy by overexpressing the disease-causing mutant caveolin-3 (CAV-3P104L) in skeletal muscle. Loss of caveolin-3 resulted in atrophic myopathy with increased sarcolemmal nNOS activity, indicating caveolin-3 binding and suppression on nNOS in myofiber. Here, we generated and characterized the double mutant mice showing both deficiency of nNOS and loss of caveolin-3 (CAV-3P104L+/+, nNOS-/-). The double-mutant mice exhibited a reduction in the muscle mass and strength in comparison with the mutant caveolin-3 mice. Thus, increased sarcolemmal nNOS activity by the loss of caveolin-3 could prevent muscle atrophy in the pathogenesis leading to LGMD1C.

Free Research Field

神経内科学