Nonprogressive transgene-related callosal and hippocampal changes in PDAPP mice.
We have previously shown that homozygous PDAPP mice, a transgenic model of Alzheimer's-like amyloidosis, have abnormal corpus callosi and anterior hippocampi. Now, we investigated the extent to which these morphological abnormalities are correlated with mutant gene dose in a larger, independent, and substantially younger cohort. Homozygous and heterozygous PDAPP mice had significantly smaller callosal commissure length and anterior hippocampal area than controls. Reductions correlated with mutant APP gene dose, with homozygotes showing the greatest reduction, and were present at 2 months of age. These findings and previous work with APP knockouts suggest that PDAPP mice have impaired white matter development due to interference with native murine APP.
Valla
Jon
J
Barrow Neurological Institute, St Joseph's Hospital & Medical Center, Phoenix, Arizona 85013, USA. jvalla@chw.edu
Schneider
Lonnie E
LE
Gonzalez-Lima
Francisco
F
Reiman
Eric M
EM
D061085:Agenesis of Corpus Callosum; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D003337:Corpus Callosum / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009421:Nervous System Malformations / Q000235:genetics / Q000503:physiopathology*; D019076:Transgenes / Q000235:genetics*
D016564:Amyloid beta-Protein Precursor