Comparative characterization of GPRC5B and GPRC5CLacZ knockin mice; behavioral abnormalities in GPRC5B-deficient mice |
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Authors: | Sano Takamitsu Kim Yeon-Jeong Oshima Eriko Shimizu Chika Kiyonari Hiroshi Abe Takaya Higashi Hideyoshi Yamada Kazuyuki Hirabayashi Yoshio |
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Institution: | aLaboratory for Molecular Membrane Neuroscience, Brain Science Institute, RIKEN, Wako-shi, Saitama 351-0198, Japan;bLaboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, 2-2-3 Minatojima Minamimachi, Chuo-ku, Kobe 650-0047, Japan;cDivision of Glyco-Signal Research Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, Miyagi 981-8558, Japan;dSupport Unit for Animal Resources Development, Research Resources Center, Brain Science Institute, RIKEN, Wako-shi, Saitama 351-0198, Japan |
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Abstract: | Although GPRC5B and GPRC5C are categorized into the G protein-coupled receptor family C, including glutamate receptors, GABA receptors, and taste receptors, their physiological functions remain unknown. Since both receptors are expressed in the brain and evolutionarily conserved from fly to human, it is conceivable that they have significant biological roles particularly in the central nervous system (CNS). We generated GPRC5B- and GPRC5C-deficient mice to examine their roles in the CNS. Both homozygous mice were viable, fertile, and showed no apparent histological abnormalities, though GPRC5B-deficient mice resulted in partial perinatal lethality. We demonstrated that the expressions of GPRC5B and GPRC5C are developmentally regulated and differentially distributed in the brain. GPRC5B-deficient mice exhibited altered spontaneous activity pattern and decreased response to a new environment, while GPRC5C-deficient mice have no apparent behavioral deficits. Thus, GPRC5B has important roles for animal behavior controlled by the CNS. In contrast, GPRC5C does not affect behavior, though it has a high sequence similarity to GPRC5B. These findings suggest that family C, group 5 (GPRC5) receptors in mammals are functionally segregated from their common ancestor. |
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Keywords: | Abbreviations: CNS central nervous system GPCRs G protein-coupled receptors |
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