CONSEQUENCES OF LACK OF BETA-1 INTEGRIN GENE-EXPRESSION IN MICE
CONSEQUENCES OF LACK OF BETA-1 INTEGRIN GENE-EXPRESSION IN MICE
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DOI：
10.1101/gad.9.15.1896
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发表时间：
1995-08-01
影响因子：
10.5
通讯作者：
MEYER, M
中科院分区：
文献类型：
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作者：
FASSLER, R;MEYER, M
β 1整联蛋白是介导细胞-细胞和细胞-基质相互作用的细胞表面受体。我们已经在小鼠和胚胎干细胞（ES）中产生了β 1整合素亚基基因的无效突变。杂合子小鼠与正常同窝出生的小鼠无法区分。纯合子无效胚胎正常发育至囊胚期，植入并侵入子宫基底膜，但此后不久死亡。使用β 1整合素缺陷的ES细胞，我们建立了嵌合胚胎和成年小鼠。嵌合体胚胎的分析表明，在所有的胚层中存在β 1整合素缺陷细胞，表明β 1无效细胞可以在正常组织的背景下分化和迁移。当在胚胎第9.5天（E9.5）进行评估时，β 1-null细胞贡献低于25%的胚胎发育正常，而贡献高于此阈值的胚胎变形并显示异常形态发生。在成年嵌合小鼠中，β 1整合素缺陷细胞未能定植于肝脏和脾脏，但在所有其他组织中发现，分析水平为2%-25%。嵌合体小鼠的免疫染色显示，在心肌中，有小的，分散的肌细胞斑块是β 1-null。相比之下，许多肌管显示出一些β 1-无效的贡献，作为野生型和突变型成肌细胞之间融合形成混合肌管的结果。成年嵌合体脑在分析的所有区域中都含有β 1-无效细胞。此外，来自神经嵴的组织含有β 1整联蛋白缺陷细胞，表明神经元细胞以及神经嵴细胞的迁移可以在β 1整联蛋白不存在的情况下发生。
beta 1 integrins are cell-surface receptors that mediate cell-cell and cell-matrix interactions. We have generated a null mutation in the gene for the beta 1 integrin subunit in mice and embryonic stem (ES) cells. Heterozygous mice are indistinguishable from normal littermates. Homozygous null embryos develop normally to the blastocyst stage, implant, and invade the uterine basement membrane but die shortly thereafter. Using beta 1 integrin-deficient ES cells we have established chimeric embryos and adult mice. Analysis of the chimeric embryos demonstrated the presence of beta 1 integrin-deficient cells in all germ layers indicating that beta 1-null cells can differentiate and migrate in a context of normal tissue. When evaluated at embryonic day 9.5 (E9.5), embryos with a beta 1-null cell contribution below 25% were developing normally, whereas embryos with a contribution above this threshold were distorted and showed abnormal morphogenesis. In adult chimeric mice beta 1 integrin-deficient cells failed to colonize liver and spleen but were found in all other tissues analyzed at levels from 2%-25%. Immunostaining of chimeric mice showed that in cardiac muscle, there were small, scattered patches of myocytes that were beta 1-null. In contrast, many myotubes showed some beta 1-null contribution as a result of fusion between wild-type and mutant myoblasts to form mixed myotubes. The adult chimeric brain contained beta 1-null cells in all regions analyzed. Also, tissues derived from the neural crest contained beta 1 integrin-deficient cells indicating that migration of neuronal cells as well as neural crest cells can occur in the absence of beta 1 integrins.