Crybb2 coding for βB2-crystallin affects sensorimotor gating and hippocampal functionReportar como inadecuado




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Mammalian Genome

, Volume 24, Issue 9–10, pp 333–348

First Online: 06 October 2013Received: 05 June 2013Accepted: 22 July 2013

Abstract

βB2-crystallin gene symbol: Crybb2-CRYBB2 was first described as a structural protein of the ocular lens. This gene, however, is also expressed in several regions of the mammalian brain, although its function in this organ remains entirely unknown. To unravel some aspects of its function in the brain, we combined behavioral, neuroanatomical, and physiological analyses in a novel Crybb2 mouse mutant, O377. Behavioral tests with male O377 mutants revealed altered sensorimotor gating, suggesting modified neuronal functions. Since these mouse mutants also displayed reduced hippocampal size, we concentrated further investigations on the hippocampus. Free intracellular Ca levels were increased and apoptosis was enhanced in the hippocampus of O377 mutants. Moreover, the expression of the gene encoding calpain 3 gene symbol Capn3 was elevated and the expression of genes coding for the NMDA receptor subunits was downregulated. Additionally, the number of parvalbumin-positive interneurons was decreased in the hippocampus but not in the cortex of the mutants. High-speed voltage-sensitive dye imaging demonstrated an increased translation of input-to-output neuronal activity in the dentate gyrus of this Crybb2 mutant. These results point to an important function of βB2-crystallin in the hippocampal network. They indicate pleiotropic effects of mutations in the Crybb2 gene, which previously had been considered to be specific to the ocular lens. Moreover, our results are the first to demonstrate that βB2-crystallin has a role in hippocampal function and behavioral phenotypes. This model can now be further explored by future experiments.

Electronic supplementary materialThe online version of this article doi:10.1007-s00335-013-9478-7 contains supplementary material, which is available to authorized users.

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Autor: Minxuan Sun - Sabine M. Hölter - Jens Stepan - Lillian Garrett - Just Genius - Elisabeth Kremmer - Martin Hrabě de Angel

Fuente: https://link.springer.com/







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