Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities

被引：117
作者：
Yamazaki, S
Iwamoto, R
Saeki, K
Asakura, M
Takashima, S
Yamazaki, A
Kimura, R
Mizushima, H
Moribe, H
Higashiyama, S
Endoh, M
Kaneda, Y
Takagi, S
Itami, S
Takeda, N
Yamada, G
Mekada, E
机构：
[1] Osaka Univ, Microbial Dis Res Inst, Dept Cell Biol, Suita, Osaka 5650871, Japan
[2] Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka 5650871, Japan
[3] Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut, Suita, Osaka 5650871, Japan
[4] Osaka Univ, Grad Sch Med, Div Gene Therapy Sci, Suita, Osaka 5650871, Japan
[5] Kyushu Univ, Med Inst Bioregulat, Fukuoka 8128582, Japan
[6] Ehime Univ, Sch Med, Dept Med Biochem, Matsuyama, Ehime 7910295, Japan
[7] Kumamoto Univ, Ctr Anim Resource & Dev, Kumamoto 8600811, Japan
[8] Kumamoto Univ, Grad Sch Mol & Genomic Pharm, Kumamoto 8600811, Japan
来源：
JOURNAL OF CELL BIOLOGY | 2003年 / 163卷 / 03期
关键词：
ectodomain shedding; ErbB; cardiomyopathy; valvulogenesis; epidermal hyperplasia; GROWTH-FACTOR; DILATED CARDIOMYOPATHY; RECEPTOR; VALVULOGENESIS; IDENTIFICATION; ORGANIZATION; JUXTACRINE; EXPRESSION; MUTANT; DOMAIN;
D O I：
10.1083/jcb.200307035
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain-truncated form (HBDeltatm) of the molecule. HBuc/uc mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On the other hand, mice carrying HBDeltatm exhibited severe hyperplasia in both skin and heart. These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control.
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收藏
页码：469 / 475
页数：7
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