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Publication : Genetic and cytologic localization of genes related to Down syndrome and Alzheimer's disease in the mouse.

First Author  Reeves RH Year  1987
Journal  Cytogenet Cell Genet Volume  46
Pages  681 (Abstr.) Mgi Jnum  J:12385
Mgi Id  MGI:60633 Citation  Reeves RH, et al. (1987) Genetic and cytologic localization of genes related to Down syndrome and Alzheimer's disease in the mouse. Cytogenet Cell Genet 46:681 (Abstr.)
abstractText  Full text of Abstract: Abstracts of workshop presentations. Genetic and cytologic localization of genes related to Down syndrome and Alzheimer's disease in the mouse. Reeves RH, Oster-Granite ML, Gearhart JD, Coyle JT, Robakis N. Departments of Physiology and Neurosciences, Johns Hopkins University School of Medicine, Baltimore, MD. NYS Institute Basic Research, Staten Island, NY. Mice trisomic for chromosome 16 (MMU 16) develop many stigmata analogous to those seen in humans with trisomy 21 (Down Syndrome, DS). Several genes found on human chromosome 21 (HSA 21) map to MMU 16 in the mouse. We have previously constructed a genetic map of six markers spanning most of the length of MMU 16 (Reeves et al. Cytogenet Cell Genet, in press), including two genes, Sod-1 and Ets-2, which map to the DS region of HSA 21. We report here that another gene from HSA 21, which encodes the Beta amyloid peptide found in the cerebrovascular and neuritic plaques characteristic of Alzheimer's disease, maps to MMU 16. The homologous mouse gene, designated provisionally cerebrovascular amyloid peptide (Cvap), was localized genetically on the backcross, (Czech II X BALB/cPt) X Czech II. It is located within 3.2 cM of the Sod-1 and Ets-2 loci (N = 94). Cytologic localization of Sod-1, Ets-2, and Cvap was accomplished using somatic cell hybrids segregating the T(2H3-4;16C3)28H translocation. Hybrids were constructed between primary fibroblasts from a T28H mouse and the Ade-C hamster cell line, which is deficient in the enzyme phosphoribosyl glycineamide synthetase (Prgs), the gene for which maps to MMU 16, band C3--ter. Cvap and Ets-2 were syntenic in hybrids rescued by the mouse Prgs enzyme, demonstrating that they are also found in the region 16C3-> ter, In contrast to a previous report (Cox and Epstein, Ann NY Acad Sci 450:169), Sod-1 segregated with markers of the proximal and not the distal end of MMU 16, indicating that it is proximal to the T28H breakpoint. Since Sod-1 has been localized to the region of MMU 16 distal to the T16H breakpoint (Francke and Taggart, Proc Natl Acad Sci USA 76:5230, 1979), we conclude that it is located in the region B5-> C3.Taken together, the tight genetic linkage between Ets-2, Cvap, and Sod-1 and the occurence of the T28H breakpoint between these genes suggests that they are close to the T28H breakpoint on MMU 16.
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