Behavioral Analysis of SNAP-25 and Synaptobrevin-2 Haploinsufficiency in Mice

Neuroscience
Lisa M MonteggiaEge T Kavalali

Abstract

In central synapses, synaptobrevin-2 (also called VAMP-2) is the predominant synaptic vesicle SNARE protein that interacts with the plasma membrane SNAREs, SNAP-25 and syntaxin-1 to execute exocytosis. Mice deficient in synaptobrevin-2 or SNAP-25 show embryonic lethality, which precludes investigation of the complete loss-of-function of these proteins in the adult nervous system. However, mice that carry heterozygous null mutations survive into adulthood and are fertile. In order to elucidate how loss-of-function mutations in these proteins may result in human disease phenotypes it is important to develop bona fide animal models. Therefore, given the importance of these two critical SNAREs in central synaptic transmission and their association with several neurological or neuropsychiatric disorders, we performed a comprehensive behavioral analysis of SNAP-25 heterozygous null (SNAP-25+/-) mice as well as the synaptobrevin-2 heterozygous null (+/-) mice. This analysis revealed only mild phenotypes, SNAP-25 (+/-) mice exhibited marked hypoactivity, whereas synaptobrevin-2 (+/-) mice showed enhanced performance on the rotarod. The two mouse lines did not manifest significant deficits in anxiety-related behaviors, learning and memo...Continue Reading

Citations

Sep 10, 2020·Human Mutation·Roxanne L SimmonsSusan M Voglmaier
Sep 12, 2020·Journal of Neurochemistry·Holly MellandSarah L Gordon
Jun 24, 2020·Brain : a Journal of Neurology·Gülçin VardarChristian Freund
Apr 4, 2021·Brain Sciences·Cong LiuDesheng Liang

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