Pituitary phenotypes of mice lacking the notch signalling ligand delta-like 1 homologue.

Pituitary phenotypes of mice lacking the notch signalling ligand delta-like 1 homologue.
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DOI:
10.1111/jne.12010
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发表时间:
2013-04
影响因子:
3.2
通讯作者:
Le Tissier PR
Le Tissier PR
中科院分区:
医学3区
文献类型:
--
作者:
Cheung LY;Rizzoti K;Lovell-Badge R;Le Tissier PR

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Notch信号通路配体δ样1同源物(Dlk 1,也称为Pref 1)在整个发育中的垂体中表达,并仅限于成年腺体内的大多数生长激素(GH)细胞。我们研究了Dlk 1在垂体发育和功能中的作用,从胚胎发育后期到成年,使用完全缺乏Dlk 1表达的小鼠模型。我们证实,Dlk 1-null小鼠较短,体重低于野生型同窝出生的小鼠从妊娠后期,分娩和成年。Dlk 1的损失导致整个生命中GH含量的显着减少,而其他垂体激素则根据性别和年龄不同程度地减少。脑垂体的大小和产生垂体的细胞群的比例都没有改变,这表明每个细胞的激素含量减少了。在体内挑战的突变体和野生型同窝出生的生长激素释放激素和生长激素释放六肽显示,GH分泌减少是不太可能占Dlk 1基因敲除动物的生长减少。这些数据表明,Dlk 1的损失引起轻微的垂体缺陷,表现为年龄和性别依赖性的垂体激素含量减少。然而,其他组织中的Dlk 1表达最有可能是突变动物中观察到的体重和长度差异的原因。
The Notch signalling pathway ligand delta-like 1 homologue (Dlk1, also named Pref1) is expressed throughout the developing pituitary and becomes restricted to mostly growth hormone (GH) cells within the adult gland. We have investigated the role of Dlk1 in pituitary development and function from late embryogenesis to adulthood using a mouse model completely lacking the expression of Dlk1. We confirm that Dlk1-null mice are shorter and weigh less than wild-type littermates from late gestation, at parturition and in adulthood. A loss of Dlk1 leads to significant reduction in GH content throughout life, whereas other pituitary hormones are reduced to varying degrees depending on sex and age. Both the size of the pituitary and the proportion of hormone-producing cell populations are unchanged, suggesting that there is a reduction in hormone content per cell. In vivo challenge of mutant and wild-type littermates with growth hormone-releasing hormone and growth hormone-releasing hexapeptide shows that reduced GH secretion is unlikely to account for the reduced growth of Dlk1 knockout animals. These data suggest that loss of Dlk1 gives rise to minor pituitary defects manifesting as an age- and sex-dependent reduction in pituitary hormone contents. However, Dlk1 expression in other tissue is most likely responsible for the weight and length differences observed in mutant animals.
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