Griffin Kurt J, Kirschner Lawrence S, Matyakhina Ludmila, Stergiopoulos Sotirios, Robinson-White Audrey, Weinberg Frank, Meoli Elise, Bornstein Stefan R, Stratakis Constantine A
Section on Genetics and Endocrinology, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland 20892-1862, USA.
Endocr Res. 2004 Nov;30(4):903-11. doi: 10.1081/erc-200044145.
Mice with complete inactivation of the type Ialpha regulatory subunit (RIalpha) of cyclic (c) AMP-dependent protein kinase (PKA) (coded by the Prkar1a gene) die early in embryonic life. To bypass the early embryonic lethality of Prkar1a-/- mice, we established transgenic mice carrying an antisense transgene for Prkar1a exon 2 (X2AS) under the control of a tetracycline-responsive promoter. Mice developed thyroid follicular hyperplasia and adenomas, adrenocortical hyperplasia, and other features reminiscent of PPNAD, and histiocytic and epithelial hyperplasias, lymphomas, and other mesenchymal tumors. This mouse provides a useful tool for the investigation of cAMP, RIalpha, and PKA functions and confirms Prkar1a's critical role in tumorigenesis in endocrine and other tissues.
环磷酸腺苷（cAMP）依赖性蛋白激酶（PKA）的Iα调节亚基（RIα）完全失活的小鼠（由Prkar1a基因编码）在胚胎早期死亡。为了绕过Prkar1a基因敲除小鼠的早期胚胎致死性，我们构建了携带四环素反应性启动子控制下的Prkar1a外显子2反义转基因（X2AS）的转基因小鼠。这些小鼠出现了甲状腺滤泡增生和腺瘤、肾上腺皮质增生以及其他类似于原发性色素沉着性结节性肾上腺皮质病（PPNAD）的特征，还有组织细胞和上皮增生、淋巴瘤以及其他间充质肿瘤。这种小鼠为研究cAMP、RIα和PKA的功能提供了有用的工具，并证实了Prkar1a在内分泌和其他组织肿瘤发生中的关键作用。
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