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左右不对称与驱动蛋白超家族蛋白KIF3A:通过对kif3A -/- 小鼠的分析在左右侧性决定和中胚层诱导方面的新见解

Left-right asymmetry and kinesin superfamily protein KIF3A: new insights in determination of laterality and mesoderm induction by kif3A-/- mice analysis.

作者信息

Takeda S, Yonekawa Y, Tanaka Y, Okada Y, Nonaka S, Hirokawa N

机构信息

Department of Cell Biology and Anatomy, University of Tokyo, Graduate School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033 Japan.

出版信息

J Cell Biol. 1999 May 17;145(4):825-36. doi: 10.1083/jcb.145.4.825.

Abstract

KIF3A is a classical member of the kinesin superfamily proteins (KIFs), ubiquitously expressed although predominantly in neural tissues, and which forms a heterotrimeric KIF3 complex with KIF3B or KIF3C and an associated protein, KAP3. To elucidate the function of the kif3A gene in vivo, we made kif3A knockout mice. kif3A-/- embryos displayed severe developmental abnormalities characterized by neural tube degeneration and mesodermal and caudal dysgenesis and died during the midgestational period at approximately 10.5 dpc (days post coitum), possibly resulting from cardiovascular insufficiency. Whole mount in situ hybridization of Pax6 revealed a normal pattern while staining by sonic hedgehog (shh) and Brachyury (T) exhibited abnormal patterns in the anterior-posterior (A-P) direction at both mesencephalic and thoracic levels. These results suggest that KIF3A might be involved in mesodermal patterning and in turn neurogenesis.

摘要

KIF3A是驱动蛋白超家族蛋白(KIFs)的经典成员,在全身广泛表达,不过主要存在于神经组织中,它与KIF3B或KIF3C以及一种相关蛋白KAP3形成异源三聚体KIF3复合物。为了阐明kif3A基因在体内的功能,我们制备了kif3A基因敲除小鼠。kif3A基因敲除小鼠胚胎表现出严重的发育异常,其特征为神经管退化以及中胚层和尾部发育不全,并在妊娠中期约10.5天胚龄(受孕后天数)时死亡,可能是由心血管功能不全导致的。Pax6的全胚胎原位杂交显示出正常模式,而在中脑和胸段水平,经音猬因子(shh)和短尾相关蛋白(T)染色后,在前后(A-P)方向上呈现出异常模式。这些结果表明,KIF3A可能参与中胚层模式形成,进而参与神经发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f495/2133177/db2ee5dcbef1/JCB9901056.f1a.jpg

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