Long-term intracerebral transplants of fetal hippocampus from mouse trisomy 16, a model for Down's syndrome (trisomy 21), do not exhibit Alzheimer's disease neuropathology by ultrastructural criteria .
Murine trisomy 16 (Ts16) is an animal model for Down's syndrome (human trisomy 21), because mouse chromosome 16 is genetically homologous to human chromosome 21. Down's syndrome patients, older than 35 years, demonstrate the neuropathological and neurochemical defects characteristic of Alzheimer's disease and Ts16 mouse fetuses exhibit phenotypic abnormalities similar to those in Down's syndrome fetuses. Trisomic mouse fetuses, however, die in utero, and so do not survive long enough for their brains to develop the degenerative changes of aging. This can be overcome by grafting the fetal Ts16 hippocampus (an early site for the development of the pathological features characteristic of Alzheimer's disease), into the cerebral ventricle or striatum of a normal adult mouse host. We have made such transplants, which have survived for up to 12 months. Examining these grafts ultrastructurally at various stages from 1 to 12 months, and comparing them with normal control grafts, reveals no structural difference that could be deemed characteristic of Alzheimer disease; no neurofibrillary tangle or senile plaque was observed. These observations, together with the normal structure of the neuronal organelles in trisomic hippocampal tissue, suggest that trisomic mouse grafts are not a useful model for Alzheimer's disease, despite earlier reports to the contrary.
Lane
N J
NJ
Department of Zoology, University of Cambridge, UK.
Balbo
A
A
Stoll
J
J
Rapoport
S I
SI
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000473:pathology*; D005260:Female; D016332:Fetal Tissue Transplantation / Q000473:pathology*; D006624:Hippocampus / Q000637:transplantation* / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013997:Time Factors; D014314:Trisomy