Disruption of the murine nuclear factor I-A gene (Nfia) results in perinatal lethality, hydrocephalus, and agenesis of the corpus callosum

被引:185
作者
das Neves, L
Duchala, CS
Godinho, F
Haxhiu, MA
Colmenares, C
Macklin, WB
Campbell, CE
Butz, KG
Gronostajski, RM
机构
[1] Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA
[2] Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA
[3] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA
[4] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA
关键词
D O I
10.1073/pnas.96.21.11946
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The phylogenetically conserved nuclear factor I (NFI) family of transcription/replication proteins is essential both for adenoviral DNA replication and for the transcription of many cellular genes. We showed previously that the four murine NFI genes (Nfia, Nfib, Nfic, and Nfix) are expressed in unique but overlapping patterns during mouse development and in adult tissues. Here we show that disruption of the Nfia gene causes perinatal lethality, with >95% of homozygous Nfia(-/-) animals dying within 2 weeks after birth. Newborn Nfia(-/-) animals lack a corpus callosum and show ventricular dilation indicating early hydrocephalus. Rare surviving homozygous Nfia(-/-) mice lack a corpus callosum, show severe communicating hydrocephalus. a full-axial tremor indicative of neurological defects, male-sterility, low female fertility, but near normal life spans. These findings indicate that while the Nfia gene appears nonessential for cell viability and DNA replication in embryonic stem cells and fibroblasts, loss of Nfia function causes severe developmental defects. This finding of an NFI gene required for a developmental process suggests that the four NFI genes may have distinct roles in vertebrate development.
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页码:11946 / 11951
页数:6
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