title: Unaltered secretion of beta-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice.
abstract: The beta-amyloid peptide, which forms extracellular cerebral deposits in Alzheimer's disease, is derived from a large membrane-spanning glycoprotein referred to as the beta-amyloid precursor protein (APP). The APP is normally cleaved within the beta-amyloid region by a putative proteinase (alpha-secretase) to generate large soluble amino-terminal derivatives of APP, and this event prevents the beta-amyloid peptide formation. It has been suggested that the gelatinase A (matrix metalloproteinase 2, a 72-kDa type IV collagenase) may act either as alpha-secretase or as beta-secretase. Mice devoid of gelatinase A generated by gene targeting develop normally, except for a subtle delay in their growth, thus providing a useful system to examine the role of gelatinase A in the cleavage and secretion of APP in vivo. We show here that APP is cleaved within the beta-amyloid region and secreted into the extracellular milieu of brain and cultured fibroblasts without gelatinase A activity. The data suggest that gelatinase A does not play an essential role in the generation and release of soluble derivatives of APP at physiological conditions.
authors.affiliation: Institute for Virus Research, Kyoto University, 53 Kawahara, Syogo-in, Sakyo-ku, Kyoto 606-01, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Gomi
authors.forename: S
authors.initials: S
authors.lastname: Nakao
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Itohara
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D018093:Gelatinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D006868:Hydrolysis; D007700:Kinetics; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D016564:Amyloid beta-Protein Precursor; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2