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 PMID:14597776  

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

Satoru Yamazaki | Ryo Iwamoto | Kazuko Saeki | Masanori Asakura | Seiji Takashima | Ayano Yamazaki | Rina Kimura | Hiroto Mizushima | Hiroki Moribe | Shigeki Higashiyama | Masayuki Endoh | Yasufumi Kaneda | Satoshi Takagi | Satoshi Itami | Naoki Takeda | Gen Yamada | Eisuke Mekada
The Journal of cell biology | 2003

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. HB(uc/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.

Pubmed ID: 14597776

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Crl:NU(NCr)-Foxn1nu (tool)

RRID:IMSR_CRL:490

Mus musculus with name Crl:NU(NCr)-Foxn1nu from IMSR.

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