Discovery of a novel murine keratin 6 (K6) isoform explains the absence of hair and nail defects in mice deficient for K6a and K6b.

Discovery of a novel murine keratin 6 (K6) isoform explains the absence of hair and nail defects in mice deficient for K6a and K6b.
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DOI:
10.1083/jcb.200102079
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发表时间:
2001-08-06
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Roop DR
Roop DR
中科院分区:
其他
文献类型:
--
作者:
Wojcik SM;Longley MA;Roop DR

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已知小鼠基因组有两个角蛋白6 (K6)基因,小鼠K6 (MK6)a和MK6b。这些基因表现出复杂的表达模式,在口腔黏膜上皮、毛囊和甲床中具有组成性表达。我们通过胚胎干细胞技术培育出了缺乏这两种基因的小鼠。大多数MK6a/b−/−小鼠在出生后的头两周内死于饥饿。这是由于舌背上皮的局部解体,导致细胞碎片斑块的积聚,严重损害进食。然而,约25%的MK6a/b−/−小鼠存活至成年。值得注意的是,存活的MK6a/b - / -小鼠有正常的毛发和指甲。令我们惊讶的是,我们在MK6a/b−/−小鼠的毛囊和甲床中都发现了MK6染色,这表明存在第三个MK6基因。我们克隆了这个以前未知的小鼠角蛋白基因,发现它与人类在毛囊中表达的K6hf高度同源。因此,我们将该基因命名为MK6毛囊(MK6hf)。MK6hf在MK6a/b−/−毛囊和指甲中的存在为MK6a/b−/−动物中没有毛发和指甲缺陷提供了解释。
The murine genome is known to have two keratin 6 (K6) genes, mouse K6 (MK6)a and MK6b. These genes display a complex expression pattern with constitutive expression in the epithelia of oral mucosa, hair follicles, and nail beds. We generated mice deficient for both genes through embryonic stem cell technology. The majority of MK6a/b−/− mice die of starvation within the first two weeks of life. This is due to a localized disintegration of the dorsal tongue epithelium, which results in the build up of a plaque of cell debris that severely impairs feeding. However, ∼25% of MK6a/b−/− mice survive to adulthood. Remarkably, the surviving MK6a/b−/− mice have normal hair and nails. To our surprise, we discovered MK6 staining both in the hair follicle and the nail bed of MK6a/b−/− mice, indicating the presence of a third MK6 gene. We cloned this previously unknown murine keratin gene and found it to be highly homologous to human K6hf, which is expressed in hair follicles. We therefore termed this gene MK6 hair follicle (MK6hf). The presence of MK6hf in the MK6a/b−/− follicles and nails offers an explanation for the absence of hair and nail defects in MK6a/b−/− animals.
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