Increased expression of laminin-1 and collagen (IV) subunits in the aganglionic bowel of ls/ls, but not c-ret -/- mice.
Increased expression of laminin-1 and collagen (IV) subunits in the aganglionic bowel of ls/ls, but not c-ret -/- mice.
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ls/ls 小鼠无神经节肠中层粘连蛋白-1 和胶原蛋白 (IV) 亚基的表达增加，但 c-ret -/- 小鼠的无神经节肠中层粘连蛋白-1 和胶原蛋白 (IV) 亚基的表达增加。
DOI：
10.1006/dbio.1996.0234
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Gershon,MD
中科院分区：
文献类型：
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作者：
Rothman,TP;Chen,J;Howard,MJ;Costantini,F;Schuchardt,A;Pachnis,V;Gershon,MD
细胞外基质分子，包括层粘连蛋白，影响肠神经元的发育，并在无神经节结肠炎/小肠中积聚。定量北方分析显示，编码层粘连蛋白β1和γ1亚基以及胶原α1（IV）和α2（IV）的mRNA在结肠中增加。用逆转录和竞争性聚合酶链反应（RT-cPCR）定量检测层粘连蛋白α1（laminin α1）的转录水平。层粘连蛋白α1转录本的丰度受发育调控，但在每一年龄段，其表达量均高于野生型结肠。原位杂交显示，结肠中编码层粘连蛋白α1和β1以及胶原α2（IV）的转录本最初表达于内胚层，但到E15时，表达转移至结肠间充质细胞（ls/ls>野生型），其中嵴源性细胞迁移。层粘连蛋白α1的表达在E15和newcanc-ret −/−小鼠的完全无神经节肠中进行了检测，以确定当神经发生失败时是否会出现增加，而与这些缺陷无关。RT-cPCR显示，E15或新生动物的ret-/-结肠中编码层粘连蛋白α1的mRNA与对照组无差异。在c-ret −/−动物中，不能检测到在新生儿/新生儿中显著的化学上可证实的层粘连蛋白的积累。这些观察结果表明，转录层粘连蛋白-1和胶原蛋白（IV）的增加，在结肠和周围的盆腔间充质的fls/lsmice，因为一个内在的病变，而不是继发性后果的无神经节细胞症。这些数据与层粘连蛋白-1的表达增加导致嵴源性细胞未能完成其在上皮/淋巴细胞上的定殖的假设是一致的。
Extracellular matrix molecules, including laminin, affect the development of enteric neurons and accumulate in the aganglionic colon ofls/lsmice. Quantitative Northern analysis revealed that mRNAs encoding the β1 and γ1 subunits of laminin and collagens α1(IV) and α2(IV) are increased in the colons ofls/lsmice. Transcripts of laminin α1 were evaluated quantitatively with reverse transcription and the competitive polymerase chain reaction (RT–cPCR). The abundance of laminin α1 transcripts was developmentally regulated, but greater in thels/lsthan the wild-type colon at each age examined.In situhybridization revealed that transcripts in the colon encoding laminin α1 and β1 and collagen α2(IV) were initially expressed in the endoderm, but by E15, expression shifted to cells of the colonic mesenchyme (ls/ls> wild type) where crest-derived cells migrate. The expression of laminin α1 was examined in the totally aganglionic intestine of E15 and newbornc-ret−/− mice, to determine whether an increase occurs when neurogenesis fails independently of thels/lsdefect. RT–cPCR revealed no difference from control in mRNA encoding laminin α1 in thec-ret−/− colon in either E15 or newborn animals. The accumulation of immunohistochemically demonstrable laminin that is prominent in the newbornls/lscolon could not be detected in that ofc-ret−/− animals. These observations suggest that transcripts encoding laminin-1 and collagen (IV) are increased in the colon and surrounding pelvic mesenchyme ofls/lsmice because of an intrinsic lesion, rather than a secondary consequence of aganglionosis. The data are compatible with the hypothesis that the increased expression of laminin-1 contributes to the failure of crest-derived cells to complete their colonization of thels/lscolon.