RhoE deficiency produces postnatal lethality, profound motor deficits and neurodevelopmental delay in mice.

摘要: Rnd proteins are a subfamily of Rho GTPases involved in the control actin cytoskeleton dynamics and other cell functions such as motility, proliferation survival. Unlike members family, lack GTPase activity therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed Central Nervous System it has role promoting neurite formation. Despite their possible relevance during development, vivo not known. To get insight into function RhoE we generated mice lacking expression by an exon trapping cassette. null (RhoE gt/gt) smaller at birth, display growth retardation early postnatal death since only half gt/gt survive beyond day (PD) 15 100% dead PD 29. show abnormal body position with profound motor impairment impaired performance most neurobehavioral tests. Null mutant hypoactive, immature locomotor pattern significant delay appearance hindlimb mature responses. Moreover, they perform worse than littermates wire suspension, vertical climbing clinging, righting reflex negative geotaxis Also, ablation results neuromuscular maturation reduction number spinal neurons. Finally, common peroneal nerve and, consequently, complete atrophy target muscles. This first model to study member proteins, revealing important Rnd3/RhoE normal development suggesting involvement this protein neurological disorders.