Impaired motor coordination in mice lacking neural recognition molecule NB-3 of the contactin/F3 subgroup

Impaired motor coordination in mice lacking neural recognition molecule NB-3 of the contactin/F3 subgroup
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DOI:
10.1002/neu.10222
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发表时间:
2003-09-01
期刊:
JOURNAL OF NEUROBIOLOGY
影响因子:
--
通讯作者:
Watanabe, K
Watanabe, K
中科院分区:
其他
文献类型:
--
作者:
Takeda, Y;Akasaka, K;Watanabe, K

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神经识别分子NB-3属于免疫球蛋白超家族的接触蛋白亚群,仅在神经系统中表达,主要在小鼠脑发育的出生后早期上调。NB-3在小脑中的表达一直增加到成年。相反,在出生后第7天,大脑中的表达下降到低水平。为了表征NB-3在体内的功能作用,我们用β -半乳糖苷酶(Lac Z)基因取代NB-3基因的一部分,产生了NB-3缺陷小鼠。杂合小鼠脑中Lac Z的表达与大鼠小脑中NB-3免疫染色模式和先前报道的NB-3转录物原位杂交模式完全重叠,表明Lac Z的表达反映了NB-3在小鼠脑中的表达。nb -3缺陷小鼠存活且可育。突变小鼠全脑各核层的形成和组织正常。运动功能行为学测试显示,在重复实验中,NB-3基因缺失小鼠在旋转杆测试中学习停留缓慢,在悬挂钢丝和水平行走杆测试中表现出平衡和前庭感觉功能障碍。相比之下,突变小鼠的抓握力与野生型小鼠没有差异。因此,nb -3缺陷小鼠的运动协调能力受损。(C) 2003 Wiley期刊有限公司
The neural recognition molecule NB-3, which belongs to the contactin subgroup of the immunoglobulin superfamily, is expressed exclusively in the nervous system and mainly upregulated at the early postnatal stage during mouse brain development. The expression of NB-3 in the cerebellum increases until adulthood. In contrast, the expression in the cerebrum declines to a low level after postnatal day 7. To characterize the functional roles of NB-3 in vivo, we generated NB-3-deficient mice by substituting a part of the NB-3 gene with the beta-galactosidase (Lac Z) gene. Complete overlap of the Lac Z expression in the heterozygous mouse brain with the NB-3 immunostaining pattern in the rat cerebellum and with the previously reported pattern of in situ hybridization of NB-3 transcripts indicated that Lac Z expression reflects the expression of NB-3 in the mouse brain. NB-3-deficient mice were viable and fertile. The formation and organization of all nuclei and layers throughout the brains of mutant mice appeared normal. Behavioral tests to examine motor function showed that the mice deficient for NB-3 were slow to learn to stay on the rotating rod in the rotorod test during repeated trials, and that they displayed dysfunction of equilibrium and vestibular senses in the wire hang and horizontal rod-walking tests. In contrast, the mutant mice showed no difference of grasp force from the wild-type mice. Thus, NB-3-deficient mice are impaired in motor coordination. (C) 2003 Wiley Periodicals, Inc.