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KMID : 0578320120340010103
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Molecules and Cells
2012 Volume.34 No. 1 p.103 ~ p.108
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A Gene Trap Knockout of the Tiam-1 Protein Re-sults in Malformation of the Early Embryonic Brain
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Yoo Soo-Yeon
Kim Yu-Jin
Lee Hae-Ryung
Park Sung-Jeong
Park Soo-Chul
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Abstract
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Tiam-1 has been implicated in the development of the central nervous system. However, the in vivo function of Tiam-1 has not been fully determined in the developing mouse brain. In this study, we generated Tiam-1 knockout mice using a Tiam-1 gene-trapped embryonic stem cell line. Insertion of a gene trap vector into a genomic site downstream of exon 5 resulted in a mutant allele encoding a truncated protein fused with the ?-geo LacZ gene. Primary mouse embryonic fibroblasts lacking Tiam-1 revealed a significant decrease in Rac activity and cell proliferation. In addition, whole-mount embryonic LacZ expression analysis demonstrated that Tiam-1 is specifically expressed in regions of the developing brain, such as the caudal telencephalon and rostral diencephalon. More importantly, mouse embryos deficient in Tiam-1 gene expression displayed a severe defect in embryonic brain development, including neural tube closure defects or a dramatic decrease in brain size. These findings suggest that embryonic Tiam-1 expression plays a critical role during early brain de-velopment in mice.
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KEYWORD
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early brain development, Rac, Tiam-1
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