Pituitary-specific Gata2 knockout:: Effects on gonadotrope and thyrotrope function
Pituitary-specific Gata2 knockout:: Effects on gonadotrope and thyrotrope function
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DOI：
10.1210/me.2005-0378
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发表时间：
2006-06-01
影响因子：
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通讯作者：
Gordon, David F.
中科院分区：
文献类型：
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作者：
Charles, Michael A.;Saunders, Thomas L.;Gordon, David F.
GATA2在发育过程中的脑垂体以及成年促性腺激素和促甲状腺激素中表达。这对促性腺激素和促甲状腺激素细胞命运的选择以及TSH的产生具有重要意义。为了验证这一想法，我们制造了一种脑垂体特异的Gata2基因敲除，设计成在存在脑垂体特异的重组酶转基因的情况下，DNA结合的锌指区域被删除。这些小鼠基本上减少了促性腺激素的分泌，并对去势挑战做出了反应，尽管这些小鼠是有生育能力的。GATA2缺乏也会影响促甲状腺功能。突变体在出生时促甲状腺细胞较少，雄性GATA2缺陷小鼠在3-9周龄时表现出生长迟缓，成年突变体在放射甲状腺切除后产生较少的TSH以应对严重的甲状腺功能减退。因此，GATA2似乎对促性腺激素和促甲状腺激素细胞的命运和维持是必不可少的，但对于最佳的促性腺激素和促甲状腺激素功能却是重要的。GATA2基因缺陷小鼠脑下垂体中GATA3转录水平升高，这表明GATA3可以补偿GATA2。
GATA2 is expressed in the pituitary during development and in adult gonadotropes and thyrotropes. It is proposed to be important for gonadotrope and thyrotrope cell fate choice and for TSH production. To test this idea, we produced a pituitary-specific knockout of Gata2, designed so that the DNA-binding zinc-finger region is deleted in the presence of a pituitary-specific recombinase transgene. These mice have reduced secretion of gonadotropins basally and in response to castration challenge, although the mice are fertile. GATA2 deficiency also compromises thyrotrope function. Mutants have fewer thyrotrope cells at birth, male Gata2-deficient mice exhibit growth delay from 3 - 9 wk of age, and adult mutants produce less TSH in response to severe hypothyroidism after radiothyroidectomy. Therefore, Gata2 appears to be dispensable for gonadotrope and thyrotrope cell fate and maintenance, but important for optimal gonadotrope and thyrotrope function. Gata2-deficient mice exhibit elevated levels of Gata3 transcripts in the pituitary gland, suggesting that GATA3 can compensate for GATA2.