MIDGESTATIONAL LETHALITY IN MICE LACKING KERATIN-8

MIDGESTATIONAL LETHALITY IN MICE LACKING KERATIN-8
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DOI:
10.1101/gad.7.7a.1191
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发表时间:
1993-07-01
影响因子:
10.5
通讯作者:
OSHIMA, RG
OSHIMA, RG
中科院分区:
生物学1区
文献类型:
--
作者:
BARIBAULT, H;PRICE, J;OSHIMA, RG

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角蛋白8 (mK8)及其伴侣角蛋白18 (mK18)是小鼠胚胎发生过程中最先表达的中间丝蛋白。它们存在于大多数胚外上皮和胚胎单层上皮,包括滋养外胚层、内脏卵黄囊、胃肠道、肺、乳腺和子宫。我们报道mK8基因的靶向零突变导致妊娠中期死亡。突变胚胎发育迟缓,内出血,胎儿肝脏红细胞异常积聚。mk8表型有94%的外显率,少数小鼠存活到成年。我们认为mK8/mK18纤维对胎儿肝脏的完整性很重要,就像特化的人表皮角蛋白对表皮的完整性一样。小鼠的这种表型不同于报道的非洲爪蟾在原肠胚形成阶段的简单上皮角蛋白的功能。在小鼠中,mK8在性交后12天发挥重要作用。
Keratin 8 (mK8) and its partner keratin 18 (mK18) are the first intermediate filament proteins expressed during mouse embryogenesis. They are found in most extraembryonic and embryonic simple epithelia, including trophectoderm, visceral yolk sac, gastrointestinal tract, lungs, mammary glands, and uterus. We report that a targeted null mutation in the mK8 gene causes mid-gestational lethality. Mutant embryos are growth retarded and suffer from internal bleeding, with an abnormal accumulation of erythrocytes in fetal livers. The mK8-phenotype has 94% penetrance, with a few mice surviving into adulthood. We suggest that mK8/mK18 filaments are important for the integrity of the fetal liver, like specialized human epidermal keratins for the integrity of the epidermis. This phenotype in mice differs from the reported function of simple epithelium keratins in Xenopus at the gastrulation stage. In mice, mK8 fulfills a vital function at 12 days postcoitum.