Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice

Junseo Oh; Rei Takahashi; Eijiro Adachi; Shunya Kondo; Shinobu Kuratomi; Akinori Noma; David B. Alexander; Hirotoshi Motoda; Akiko Okada; Motoharu Seiki; Takeshi Itoh; Shigeyoshi Itohara; Chiaki Takahashi; Makoto Noda

doi:10.1038/sj.onc.1207688

Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice

Junseo Oh, Rei Takahashi, Eijiro Adachi, Shunya Kondo, Shinobu Kuratomi, Akinori Noma, David B. Alexander, Hirotoshi Motoda, Akiko Okada, Motoharu Seiki, Takeshi Itoh, Shigeyoshi Itohara, Chiaki Takahashi, Makoto Noda

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

113 Citations (Scopus)

Abstract

The matrix metalloproteinase (MMP) family (≃25 members in mammals) has been implicated in extracellular matrix remodeling associated with embryonic development, cancer formation and progression, and various other physiological and pathological events. Inactivating mutations in individual matrix metalloproteinase genes in mice described so far, however, are nonlethal at least up to the first few weeks after birth, suggesting functional redundancy among MMP family members. Here, we report that mice lacking two MMPs, MMP-2 (nonmembrane type) and MT1-MMP (membrane type), die immediately after birth with respiratory failure, abnormal blood vessels, and immature muscle fibers reminiscent of central core disease. In the absence of MMP-2 and MT1-MMP, myoblast fusion in vitro is also significantly retarded. These findings suggest functional overlap in mice between the two MMPs with distinct molecular natures.

Original language	English
Pages (from-to)	5041-5048
Number of pages	8
Journal	Oncogene
Volume	23
Issue number	29
DOIs	https://doi.org/10.1038/sj.onc.1207688
Publication status	Published - 2004 Jun 24

Keywords

Angiogenesis
MMP-2
MT1-MMP
Myogenesis

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.onc.1207688

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@article{779ffdd478d04df4859f8af8d2945481,

title = "Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice",

abstract = "The matrix metalloproteinase (MMP) family (≃25 members in mammals) has been implicated in extracellular matrix remodeling associated with embryonic development, cancer formation and progression, and various other physiological and pathological events. Inactivating mutations in individual matrix metalloproteinase genes in mice described so far, however, are nonlethal at least up to the first few weeks after birth, suggesting functional redundancy among MMP family members. Here, we report that mice lacking two MMPs, MMP-2 (nonmembrane type) and MT1-MMP (membrane type), die immediately after birth with respiratory failure, abnormal blood vessels, and immature muscle fibers reminiscent of central core disease. In the absence of MMP-2 and MT1-MMP, myoblast fusion in vitro is also significantly retarded. These findings suggest functional overlap in mice between the two MMPs with distinct molecular natures.",

keywords = "Angiogenesis, MMP-2, MT1-MMP, Myogenesis",

author = "Junseo Oh and Rei Takahashi and Eijiro Adachi and Shunya Kondo and Shinobu Kuratomi and Akinori Noma and Alexander, {David B.} and Hirotoshi Motoda and Akiko Okada and Motoharu Seiki and Takeshi Itoh and Shigeyoshi Itohara and Chiaki Takahashi and Makoto Noda",

note = "Funding Information: We thank Emi N ishimoto, Takashi Kawai, and Mari Kojima for technical assistance; Yukio Imamura, Yoko Morioka, Michiko Echizenya, Shu Liang Shi, and Kei-ichi Inoue for help in animal maintenance; and Aki Miyazaki and Keiko Shimizu for secretarial assistance. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan.",

year = "2004",

month = jun,

day = "24",

doi = "10.1038/sj.onc.1207688",

language = "English",

volume = "23",

pages = "5041--5048",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "29",

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TY - JOUR

T1 - Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice

AU - Oh, Junseo

AU - Takahashi, Rei

AU - Adachi, Eijiro

AU - Kondo, Shunya

AU - Kuratomi, Shinobu

AU - Noma, Akinori

AU - Alexander, David B.

AU - Motoda, Hirotoshi

AU - Okada, Akiko

AU - Seiki, Motoharu

AU - Itoh, Takeshi

AU - Itohara, Shigeyoshi

AU - Takahashi, Chiaki

AU - Noda, Makoto

N1 - Funding Information: We thank Emi N ishimoto, Takashi Kawai, and Mari Kojima for technical assistance; Yukio Imamura, Yoko Morioka, Michiko Echizenya, Shu Liang Shi, and Kei-ichi Inoue for help in animal maintenance; and Aki Miyazaki and Keiko Shimizu for secretarial assistance. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan.

PY - 2004/6/24

Y1 - 2004/6/24

N2 - The matrix metalloproteinase (MMP) family (≃25 members in mammals) has been implicated in extracellular matrix remodeling associated with embryonic development, cancer formation and progression, and various other physiological and pathological events. Inactivating mutations in individual matrix metalloproteinase genes in mice described so far, however, are nonlethal at least up to the first few weeks after birth, suggesting functional redundancy among MMP family members. Here, we report that mice lacking two MMPs, MMP-2 (nonmembrane type) and MT1-MMP (membrane type), die immediately after birth with respiratory failure, abnormal blood vessels, and immature muscle fibers reminiscent of central core disease. In the absence of MMP-2 and MT1-MMP, myoblast fusion in vitro is also significantly retarded. These findings suggest functional overlap in mice between the two MMPs with distinct molecular natures.

AB - The matrix metalloproteinase (MMP) family (≃25 members in mammals) has been implicated in extracellular matrix remodeling associated with embryonic development, cancer formation and progression, and various other physiological and pathological events. Inactivating mutations in individual matrix metalloproteinase genes in mice described so far, however, are nonlethal at least up to the first few weeks after birth, suggesting functional redundancy among MMP family members. Here, we report that mice lacking two MMPs, MMP-2 (nonmembrane type) and MT1-MMP (membrane type), die immediately after birth with respiratory failure, abnormal blood vessels, and immature muscle fibers reminiscent of central core disease. In the absence of MMP-2 and MT1-MMP, myoblast fusion in vitro is also significantly retarded. These findings suggest functional overlap in mice between the two MMPs with distinct molecular natures.

KW - Angiogenesis

KW - MMP-2

KW - MT1-MMP

KW - Myogenesis

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DO - 10.1038/sj.onc.1207688

M3 - Article

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AN - SCOPUS:3042818822

SN - 0950-9232

VL - 23

SP - 5041

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ER -

Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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