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Publication : Defective brain development in mice lacking the Hif-1alpha gene in neural cells.

First Author  Tomita S Year  2003
Journal  Mol Cell Biol Volume  23
Issue  19 Pages  6739-49
PubMed ID  12972594 Mgi Jnum  J:85763
Mgi Id  MGI:2676530 Doi  10.1128/MCB.23.19.6739-6749.2003
Citation  Tomita S, et al. (2003) Defective brain development in mice lacking the Hif-1alpha gene in neural cells. Mol Cell Biol 23(19):6739-49
abstractText  Hypoxia-inducible factor 1alpha (HIF-1alpha) is essential for vascular development during embryogenesis and pathogenesis. However, little is known about its role in brain development. To investigate the function of HIF-1alpha in the central nervous system, a conditional knockout mouse was made with the Cre/LoxP system with a nestin promoter-driven Cre. Neural cell-specific HIF-1alpha-deficient mice exhibit hydrocephalus accompanied by a reduction in neural cells and an impairment of spatial memory. Apoptosis of neural cells coincided with vascular regression in the telencephalon of mutant embryos, and these embryonic defects were successfully restored by in vivo gene delivery of HIF-1alpha to the embryos. These results showed that expression of HIF-1alpha in neural cells was essential for normal development of the brain and established a mouse model that would be useful for the evaluation of therapeutic strategies for ischemia, including hypoxia-mediated hydrocephalus.
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