title: beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity.
abstract: In several pedigrees of early onset familial Alzheimer's disease (FAD), point mutations in the beta-amyloid precursor protein (APP) gene are genetically linked to the disease. This finding implicates APP in the pathogenesis of Alzheimer's disease in these individuals. To understand the in vivo function of APP and its processing, we have generated an APP-null mutation in mice. Homozygous APP-deficient mice were viable and fertile. However, the mutant animals weighed 15%-20% less than age-matched wild-type controls. Neurological evaluation showed that the APP-deficient mice exhibited a decreased locomotor activity and forelimb grip strength, indicating a compromised neuronal or muscular function. In addition, four out of six homozygous mice showed reactive gliosis at 14 weeks of age, suggesting an impaired neuronal function as a result of the APP-null mutation.
authors.affiliation: Department of Genetics and Molecular Biology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.forename: M
authors.initials: M
authors.lastname: Jiang
authors.forename: M E
authors.initials: ME
authors.lastname: Trumbauer
authors.forename: D J
authors.initials: DJ
authors.lastname: Sirinathsinghji
authors.forename: R
authors.initials: R
authors.lastname: Hopkins
authors.forename: D W
authors.initials: DW
authors.lastname: Smith
authors.forename: R P
authors.initials: RP
authors.lastname: Heavens
authors.forename: G R
authors.initials: GR
authors.lastname: Dawson
authors.forename: S
authors.initials: S
authors.lastname: Boyce
authors.forename: M W
authors.initials: MW
authors.lastname: Conner
authors.forename: K A
authors.initials: KA
authors.lastname: Stevens
authors.forename: H H
authors.initials: HH
authors.lastname: Slunt
authors.forename: S S
authors.initials: SS
authors.lastname: Sisoda
authors.forename: H Y
authors.initials: HY
authors.lastname: Chen
authors.forename: L H
authors.initials: LH
authors.lastname: Van der Ploeg
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D005911:Gliosis / Q000235:genetics*; D008124:Locomotion / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains
chemical_list: D016564:Amyloid beta-Protein Precursor