Krapp A, Knöfler M, Ledermann B, Bürki K, Berney C, Zoerkler N, Hagenbüchle O, Wellauer P K
Swiss Institute for Experimental Cancer Research, CH-1066 Epalinges, Switzerland.
Genes Dev. 1998 Dec 1;12(23):3752-63. doi: 10.1101/gad.12.23.3752.
We have generated a mouse bearing a null allele of the gene encoding basic helix-loop-helix (bHLH) protein p48, the cell-specific DNA-binding subunit of hetero-oligomeric transcription factor PTF1 that directs the expression of genes in the exocrine pancreas. The null mutation, which establishes a lethal condition shortly after birth, leads to a complete absence of exocrine pancreatic tissue and its specific products, indicating that p48 is required for differentiation and/or proliferation of the exocrine cell lineage. p48 is so far the only developmental regulator known to be required exclusively for committing cells to an exocrine fate. The hormone secreting cells of all four endocrine lineages are present in the mesentery that normally harbors the pancreatic organ until day 16 of gestation. Toward the end of embryonic life, cells expressing endocrine functions are no longer detected at their original location but are now found to colonize the spleen, where they persist in a functional state until postnatal death of the organism occurs. These findings suggest that the presence of the exocrine pancreas is required for the correct spatial assembly of the endocrine pancreas and that, in its absence, endocrine cells are directed by default to the spleen, a site that, in some reptiles, harbors part of this particular cellular compartment.
我们培育出了一种小鼠，其携带编码碱性螺旋-环-螺旋（bHLH）蛋白p48基因的无效等位基因，p48是异源寡聚转录因子PTF1的细胞特异性DNA结合亚基，该转录因子指导外分泌胰腺中基因的表达。这种无效突变在出生后不久就会导致致命状况，会使外分泌胰腺组织及其特定产物完全缺失，这表明p48是外分泌细胞谱系分化和/或增殖所必需的。到目前为止，p48是已知唯一专门用于使细胞定向分化为外分泌命运的发育调节因子。在妊娠第16天之前，所有四个内分泌谱系的激素分泌细胞都存在于通常容纳胰腺器官的肠系膜中。在胚胎发育后期，不再能在其原始位置检测到具有内分泌功能的细胞，而是发现它们定植于脾脏，在那里它们一直保持功能状态，直到机体出生后死亡。这些发现表明，外分泌胰腺的存在是内分泌胰腺正确空间组装所必需的，并且在没有外分泌胰腺的情况下，内分泌细胞默认被引导至脾脏，在某些爬行动物中，脾脏是这个特定细胞区室的一部分所在位置。
