Hirotsune S, Takahara T, Sasaki N, Hirose K, Yoshiki A, Ohashi T, Kusakabe M, Murakami Y, Muramatsu M, Watanabe S
Genome Science Laboratory, Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.
Nat Genet. 1995 May;10(1):77-83. doi: 10.1038/ng0595-77.
We have identified a strong candidate cDNA for the mouse reeler gene. This 5 kb transcript encodes a 99.4 kD protein consisting of 881 amino acids and possessing two EGF-like motifs. We assayed two independent mutant alleles--'Jackson reeler', which has a deletion of the entire gene, and 'Orleans reeler' which exhibits a 220 bp deletion in the open reading frame, including the second EGF-like motif and resulting in a frame shift. In situ hybridization reveals that the transcript is detected exclusively in the pioneer neurons which guide neuronal cell migration along the radial array. Our findings offer an explanation for how the reeler mutant phenotype causes a disturbance of the complex architecture of the neuronal network.
我们已经鉴定出一个强有力的小鼠reeler基因候选cDNA。这个5kb的转录本编码一个由881个氨基酸组成、具有两个表皮生长因子（EGF）样基序的99.4kD蛋白质。我们检测了两个独立的突变等位基因——“杰克逊reeler”，其整个基因缺失；以及“奥尔良reeler”，其开放阅读框中有220bp的缺失，包括第二个EGF样基序，导致移码。原位杂交显示，该转录本仅在引导神经元细胞沿放射状排列迁移的先驱神经元中被检测到。我们的研究结果为reeler突变体表型如何导致神经网络复杂结构紊乱提供了解释。
