Genetic linkage in the mouse of genes involved in down syndrome and Alzheimer's disease in man

Roger H. Reeves, Nikolaos K. Robakis, Mary Lou Oster-Granite, Henryk M. Wisniewski, Joseph T. Coyle, John D. Gearhart

Research output: Contribution to journalArticle

Abstract

Recently, the gene encoding the cerebrovascular and neuritic plaque amyloid, a pathologic stigma of Alzheimer's disease (AD), has been molecularly cloned and mapped to human chromosome 21, band q21. Changes in the brains of individuals with trisomy 21 (Down syndrome, DS) over 35 years of age closely resemble AD neuropathology. Genetic homology which exists between human chromosome 21 (HSA 21) and mouse chromosome 16 (MMU 16) has led to the use of mice with trisomy 16 as a model system for studies relevant to DS. Mice with Ts16 exhibit numerous developmental abnormalities that can be correlated with features observed in DS, including neurochemical and neuroanatomic alterations. In this study, we show that the genetic homology between HSA 21 and MMU 16 extends to the gene encoding the amyloid peptide. The homologous mouse gene, designated Cvap, for cerebrovascular amyloid peptide, is localized on MMU 16 band C3 → ter, and is in close proximity to both superoxide dismutase-1 (Sod-1), and the protooncogene, Ets-2, two of the genes known to localize to the DS region of HSA 21. Linkage of these genes has been maintained since the divergence of the common ancestor of mouse and man, despite a chromosomal rearrangement which has changed the gene order between the two species. These findings expand the region of HSA 21 with known homology to MMU 16, and provide a genetic basis to suggest that studies of the trisomy 16 mouse, in addition to being relevant to DS, may also clarify the role of abnormal gene expression in AD.

Original languageEnglish (US)
Pages (from-to)215-221
Number of pages7
JournalMolecular Brain Research
Volume2
Issue number3
DOIs
StatePublished - Sep 1987

Keywords

  • Alzheimer's disease
  • Amyloid
  • Down syndrome
  • Gene mapping
  • Trisomy 16 mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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    Reeves, R. H., Robakis, N. K., Oster-Granite, M. L., Wisniewski, H. M., Coyle, J. T., & Gearhart, J. D. (1987). Genetic linkage in the mouse of genes involved in down syndrome and Alzheimer's disease in man. Molecular Brain Research, 2(3), 215-221. https://doi.org/10.1016/0169-328X(87)90028-3