Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice
Pituitary hypoplasia and respiratory distress syndrome in Prop1 knockout mice
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DOI：
10.1093/hmg/ddh311
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发表时间：
2004-11-15
影响因子：
3.5
通讯作者：
Camper, SA
中科院分区：
文献类型：
--
作者：
Nasonkin, IO;Ward, RD;Camper, SA
垂体前叶发育所需的几种同源结构域转录因子之一PIT1（Prop 1）的先知突变是人类MPHD（多种垂体激素缺乏症）的主要原因。我们发现，Prop1基因的缺失会导致小鼠严重的垂体发育不全，整个Pit1谱系失败，促性腺激素发育延迟。垂体激素缺乏会导致继发性内分泌问题以及因呼吸窘迫导致的围产期死亡率很高。突变体中的肺不张与NKX2.1和表面活性剂水平降低相关。空等位基因或自发性亚型等位基因纯合子小鼠的致死率受到遗传背景的强烈影响。Prop1基因敲除小鼠是一种很好的MPHD模型，可能有助于测试新生儿呼吸窘迫药物干预的疗效。
Mutations in Prophet of PIT1 (Prop1), one of several homeodomain transcription factors that are required for the development of the anterior pituitary gland, are the predominant cause of MPHD (multiple pituitary hormone deficiency) in humans. We show that deletion of Prop1 in mice causes severe pituitary hypoplasia with failure of the entire Pit1 lineage and delayed gonadotrope development. The pituitary hormone deficiencies cause secondary endocrine problems and a high rate of perinatal mortality due to respiratory distress. Lung atelectasis in mutants correlates with reduced levels of NKX2.1 and surfactant. Lethality of mice homozygous for either the null allele or a spontaneous hypomorphic allele is strongly influenced by genetic background. Prop1-null mice are an excellent model for MPHD and may be useful for testing the efficacy of pharmaceutical intervention for neonatal respiratory distress.