RT Journal Article SR Electronic T1 Neuroaxonal Dystrophy Caused by Group VIA Phospholipase A2 Deficiency in Mice: A Model of Human Neurodegenerative Disease JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 2212 OP 2220 DO 10.1523/JNEUROSCI.4354-07.2008 VO 28 IS 9 A1 Shinzawa, Koei A1 Sumi, Hisae A1 Ikawa, Masahito A1 Matsuoka, Yosuke A1 Okabe, Masaru A1 Sakoda, Saburo A1 Tsujimoto, Yoshihide YR 2008 UL http://www.jneurosci.org/content/28/9/2212.abstract AB Calcium-independent group VIA phospholipase A2 (iPLA2β) is considered to play a role in signal transduction and maintenance of homeostasis or remodeling of membrane phospholipids. A role of iPLA2β has been suggested in various physiological and pathological processes, including immunity, chemotaxis, and cell death, but the details remain unclear. Accordingly, we investigated mice with targeted disruption of the iPLA2β gene. iPLA2β−/− mice developed normally and grew to maturity, but all showed evidence of severe motor dysfunction, including a hindlimb clasping reflex during tail suspension, abnormal gait, and poor performance in the hanging wire grip test. Neuropathological examination of the nervous system revealed widespread degeneration of axons and/or synapses, accompanied by the presence of numerous spheroids (swollen axons) and vacuoles. These findings provide evidence that impairment of iPLA2β causes neuroaxonal degeneration, and indicate that the iPLA2β−/− mouse is an appropriate animal model of human neurodegenerative diseases associated with mutations of the iPLA2β gene, such as infantile neuroaxonal dystrophy and neurodegeneration with brain iron accumulation.