Andersen B, Pearse R V, Jenne K, Sornson M, Lin S C, Bartke A, Rosenfeld M G
Howard Hughes Medical Institute, School and Department of Medicine, University of California, San Diego, La Jolla 92093-0648, USA.
Dev Biol. 1995 Dec;172(2):495-503. doi: 10.1006/dbio.1995.8040.
The tissue-specific POU domain transcription factor Pit-1 is required for phenotypic specification of three cell types in the anterior pituitary gland of mammals: somatotropes, thyrotropes, and lactotropes. Mutations in the Pit-1 gene, as first described in Snell and Jackson dwarf (dw) mice, led to pituitary hypoplasia due to lack of these three cell types, as well as hypothyroidism and dwarfism because of deficiency of thyroid-stimulating hormone and growth hormone, respectively. The Ames dwarf (df) exhibits a phenotype identical to that of Pit-1 mutated mice but the defective gene has been mapped to a locus on mouse chromosome 11, distinct from the Pit-1 gene located on mouse chromosome 6. Our studies indicate that initial activation of the Pit-1 gene is deficient in the Ames dwarf. This suggests that the df gene is required for activation of the Pit-1 gene and provides evidence for a hierarchy of tissue-specific factors required for cellular commitment in the anterior pituitary gland.
组织特异性POU结构域转录因子Pit-1是哺乳动物垂体前叶中三种细胞类型（生长激素细胞、促甲状腺激素细胞和催乳激素细胞）表型特化所必需的。正如最初在Snell和Jackson侏儒（dw）小鼠中所描述的那样，Pit-1基因突变导致垂体发育不全，原因是缺乏这三种细胞类型，同时分别由于促甲状腺激素和生长激素缺乏而导致甲状腺功能减退和侏儒症。Ames侏儒（df）表现出与Pit-1突变小鼠相同的表型，但缺陷基因已被定位到小鼠11号染色体上的一个位点，与位于小鼠6号染色体上的Pit-1基因不同。我们的研究表明，Ames侏儒中Pit-1基因的初始激活存在缺陷。这表明df基因是激活Pit-1基因所必需的，并为垂体前叶细胞定向分化所需的组织特异性因子层次结构提供了证据。
