title: Mutations in two matrix metalloproteinase genes, MMP-2 and MT1-MMP, are synthetic lethal in mice.
abstract: The matrix metalloproteinase (MMP) family (approximately 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.
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Junseo
authors.initials: J
authors.lastname: Oh
authors.forename: Rei
authors.initials: R
authors.lastname: Takahashi
authors.forename: Eijiro
authors.initials: E
authors.lastname: Adachi
authors.forename: Shunya
authors.initials: S
authors.lastname: Kondo
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kuratomi
authors.forename: Akinori
authors.initials: A
authors.lastname: Noma
authors.forename: David B
authors.initials: DB
authors.lastname: Alexander
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Motoda
authors.forename: Akiko
authors.initials: A
authors.lastname: Okada
authors.forename: Motoharu
authors.initials: M
authors.lastname: Seiki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Itoh
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Chiaki
authors.initials: C
authors.lastname: Takahashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Noda
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000196:embryology* / Q000473:pathology*; D005804:Genes, Lethal; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000196:embryology* / Q000473:pathology; D009154:Mutation; D032446:Myoblasts / Q000473:pathology; D009389:Neovascularization, Pathologic
chemical_list: C507096:Mmp14 protein, mouse; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14