A gene trap knockout of the Tiam-1 protein results in malformation of the early embryonic brain.
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 β-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 development in mice.
Department of Biological Science, Sookmyung Women's University, Seoul 140-742, Korea.
Sooyeon
S
Yoo
Yujin
Y
Kim
Haeryung
H
Lee
Sungjeong
S
Park
Soochul
S
Park
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D053595:Embryonic Stem Cells / Q000637:transplantation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D055786:Gene Knockout Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D054220:Malformations of Cortical Development / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016548:Prosencephalon / Q000002:abnormalities* / Q000196:embryology* / Q000473:pathology; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1
D020662:Guanine Nucleotide Exchange Factors; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C513260:Tiam1 protein, mouse