Embryonic lethality of molecular chaperone hsp47 knockout mice is associated with defects in collagen biosynthesis.
Embryonic lethality of molecular chaperone hsp47 knockout mice is associated with defects in collagen biosynthesis.
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DOI：
10.1083/jcb.150.6.1499
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发表时间：
2000-09-18
期刊：
影响因子：
--
通讯作者：
Nagata K
中科院分区：
文献类型：
--
作者：
Nagai N;Hosokawa M;Itohara S;Adachi E;Matsushita T;Hosokawa N;Nagata K
前胶原在c -前肽的三个α-链组装后形成三螺旋结构，是精细结构如纤维和网状结构的先决条件。Hsp47是一种内质网应激诱导的糖蛋白，可以特异性和短暂地结合到新合成的前胶原上。然而，Hsp47在胶原生物合成中的真正功能在体内和体外均未被阐明。在这里，我们描述了Hsp47基因敲除小鼠的建立，这些小鼠在间质组织中严重缺乏成熟的、前肽加工形式的α1(I)胶原和纤维结构。IV型胶原的分子形态也受到影响，纯合子的基底膜中断。纯合子小鼠不能存活超过交媾后11.5天（dpc），上皮组织定向异常，血管破裂。用蛋白酶消化法检测培养细胞分泌的I型胶原蛋白的三螺旋形成情况，发现Hsp47+/+和Hsp47+/−细胞的胶原具有耐药性，而Hsp47−/−细胞的胶原具有敏感性。这些结果首次表明，如果没有分子伴侣Hsp47的帮助，I型胶原不能形成刚性的三螺旋结构，而小鼠的正常发育需要Hsp47。
Triple helix formation of procollagen after the assembly of three α-chains at the C-propeptide is a prerequisite for refined structures such as fibers and meshworks. Hsp47 is an ER-resident stress inducible glycoprotein that specifically and transiently binds to newly synthesized procollagens. However, the real function of Hsp47 in collagen biosynthesis has not been elucidated in vitro or in vivo. Here, we describe the establishment of Hsp47 knockout mice that are severely deficient in the mature, propeptide-processed form of α1(I) collagen and fibril structures in mesenchymal tissues. The molecular form of type IV collagen was also affected, and basement membranes were discontinuously disrupted in the homozygotes. The homozygous mice did not survive beyond 11.5 days postcoitus (dpc), and displayed abnormally orientated epithelial tissues and ruptured blood vessels. When triple helix formation of type I collagen secreted from cultured cells was monitored by protease digestion, the collagens of Hsp47+/+ and Hsp47+/− cells were resistant, but those of Hsp47−/− cells were sensitive. These results indicate for the first time that type I collagen is unable to form a rigid triple-helical structure without the assistance of molecular chaperone Hsp47, and that mice require Hsp47 for normal development.
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影响因子：
4
作者：
PELTONEN, L;HALILA, R;RYHANEN, L
通讯作者：
RYHANEN, L
影响因子：
64.5
作者：
LOHLER, J;TIMPL, R;JAENISCH, R
通讯作者：
JAENISCH, R
DOI：
10.1111/j.1432-1033.1980.tb04610.x
发表时间：
1980-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BACHINGER, HP;BRUCKNER, P;ENGEL, J
通讯作者：
ENGEL, J
影响因子：
10.5
作者：
Cosgrove, D;Meehan, DT;Samuelson, GC
通讯作者：
Samuelson, GC
影响因子：
15.9
作者：
MASUDA, H;FUKUMOTO, M;NAGATA, K
通讯作者：
NAGATA, K