Analysis Tools
mortality/aging
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• approximately 2% of expected homozygous null pups survive birth; however, these mice remain severely runted and die after 7-10 days
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• homozygous null mice die perinatally
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cellular
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• cultured cortical neurons from homozygous null mice show subtle differences in the level of hypoxic target gene induction
• following 16 hours of hypoxic treatment, transcript levels of HIF1 target genes are induced in null neurons to only 75% of wild-type levels, suggesting that ARNT2/HIF1A complexes can regulate oxygen-responsive genes
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nervous system
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• whole-mount immunohistochemistry on embryonic CNS showed no differences between wild-type and null embryos, suggesting that the expression of Vegfa and other HIF1 target genes is effectively normal
• in support of this hypothesis, homozygous null embryos display no other morphological or vascular defects
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• homozygotes display impaired hypothalamic development as shown by the loss of neuroendocrine cell-specific gene expression
• transcripts marking parvocellular and magnocellular neurons are downregulated in the mutant hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON)
• the expression of a POU-domain transcription factor required for the development of arginine-vasopressin, oxytocin, and corticotropin-releasing hormone-producing neurons is also downregulated in the mutant PVN and SON
• however, the presence of residual ARNT/HIF1A complexes is apparently sufficient to maintain steady-state target gene expression in vivo under conditions of physiological hypoxia
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