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

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 repla...

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Autores principales: Yamazaki, Satoru, Iwamoto, Ryo, Saeki, Kazuko, Asakura, Masanori, Takashima, Seiji, Yamazaki, Ayano, Kimura, Rina, Mizushima, Hiroto, Moribe, Hiroki, Higashiyama, Shigeki, Endoh, Masayuki, Kaneda, Yasufumi, Takagi, Satoshi, Itami, Satoshi, Takeda, Naoki, Yamada, Gen, Mekada, Eisuke
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173637/
https://www.ncbi.nlm.nih.gov/pubmed/14597776
http://dx.doi.org/10.1083/jcb.200307035
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author Yamazaki, Satoru
Iwamoto, Ryo
Saeki, Kazuko
Asakura, Masanori
Takashima, Seiji
Yamazaki, Ayano
Kimura, Rina
Mizushima, Hiroto
Moribe, Hiroki
Higashiyama, Shigeki
Endoh, Masayuki
Kaneda, Yasufumi
Takagi, Satoshi
Itami, Satoshi
Takeda, Naoki
Yamada, Gen
Mekada, Eisuke
author_facet Yamazaki, Satoru
Iwamoto, Ryo
Saeki, Kazuko
Asakura, Masanori
Takashima, Seiji
Yamazaki, Ayano
Kimura, Rina
Mizushima, Hiroto
Moribe, Hiroki
Higashiyama, Shigeki
Endoh, Masayuki
Kaneda, Yasufumi
Takagi, Satoshi
Itami, Satoshi
Takeda, Naoki
Yamada, Gen
Mekada, Eisuke
author_sort Yamazaki, Satoru
collection PubMed
description 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 (HB(uc)) or a transmembrane domain–truncated form (HB(Δtm)) 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 HB(Δtm) 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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spelling pubmed-21736372008-05-01 Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities Yamazaki, Satoru Iwamoto, Ryo Saeki, Kazuko Asakura, Masanori Takashima, Seiji Yamazaki, Ayano Kimura, Rina Mizushima, Hiroto Moribe, Hiroki Higashiyama, Shigeki Endoh, Masayuki Kaneda, Yasufumi Takagi, Satoshi Itami, Satoshi Takeda, Naoki Yamada, Gen Mekada, Eisuke J Cell Biol Report 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 (HB(uc)) or a transmembrane domain–truncated form (HB(Δtm)) 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 HB(Δtm) 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. The Rockefeller University Press 2003-11-10 /pmc/articles/PMC2173637/ /pubmed/14597776 http://dx.doi.org/10.1083/jcb.200307035 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Report
Yamazaki, Satoru
Iwamoto, Ryo
Saeki, Kazuko
Asakura, Masanori
Takashima, Seiji
Yamazaki, Ayano
Kimura, Rina
Mizushima, Hiroto
Moribe, Hiroki
Higashiyama, Shigeki
Endoh, Masayuki
Kaneda, Yasufumi
Takagi, Satoshi
Itami, Satoshi
Takeda, Naoki
Yamada, Gen
Mekada, Eisuke
Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities
title Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities
title_full Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities
title_fullStr Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities
title_full_unstemmed Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities
title_short Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities
title_sort mice with defects in hb-egf ectodomain shedding show severe developmental abnormalities
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173637/
https://www.ncbi.nlm.nih.gov/pubmed/14597776
http://dx.doi.org/10.1083/jcb.200307035
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