Transplants of mouse trisomy 16 hippocampus provide a model of Alzheimer's disease neuropathology.
Alzheimer's disease, which is characterized by amyloid plaques and neurofibrillary tangles, may be attributed to the abnormal expression of gene(s) located on human chromosome 21. Genetic linkage studies have narrowed the region of candidate genes to 21q11.2-21q22 of the long arm of this chromosome. Several single copy sequences within this region, including the amyloid precursor protein (APP), have been mapped to mouse chromosome 16. Reliable strategies exist for breeding Trisomy 16 mice. However, the consequences of developmental overexpression of genes on chromosome 16 have not been previously investigated, because of the lethal effects of this aneuploidy during gestation. In the present report, we employ neural transplantation to study long-term survival and pathogenesis in Trisomy 16 central nervous system tissues. Immunocytochemical staining with antiserum raised against the synthetic APP, beta-A4 and alpha 1-antichymotrypsin revealed numerous densely stained cells within hippocampal grafts of Trisomy 16 mice. Similarly, a population of grafted cells were positively stained following incubation with an antiserum raised against components of the pathological neurofibrillary tangle and with the monoclonal antibodies Tau 6.423 and ubiquitin.
Richards
S J
SJ
MRC Molecular Genetics Unit, Cambridge, UK.
Waters
J J
JJ
Beyreuther
K
K
Masters
C L
CL
Wischik
C M
CM
Sparkman
D R
DR
White
C L
CL
Abraham
C R
CR
Dunnett
S B
SB
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D016380:Brain Tissue Transplantation; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D004195:Disease Models, Animal; D005260:Female; D016332:Fetal Tissue Transplantation; D006624:Hippocampus / Q000473:pathology* / Q000637:transplantation; D006801:Humans; D007621:Karyotyping; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D011498:Protein Precursors / Q000032:analysis; D012016:Reference Values; D014314:Trisomy
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011498:Protein Precursors