Ts65Dn - localization of the translocation breakpoint and trisomic gene content in a mouse model for Down syndrome

Fluorescent in situ hybridization (FISH) - using mouse chromosome paints. p robes for the mouse major centromeric satellite DNA, and probes for genes o n chromosomes (Chr) 16 and 17 - was employed to locate the breakpoint in a translocation used to produce a mouse model for Down syndrome. The Ts65Dn t risomy is derived from the reciprocal translocation T(16:17)65Dn. The Ts65D n mouse carries a marker chromosome containing the distal segment of Chr 16 , a region that shows linkage conservation with human Chr 21, and the proxi mal end of Chr 17. This chromosome confers trisomy for most of the genes in the Chr 16 segment and Ts65Dn mice show many of the phenotypic features ch aracteristic of Down syndrome. We used FISH on metaphase chromosomes from t ranslocation T65Dn/+ heterozygotes and Ts65Dn mice to show that the Chr 17 breakpoint is distal to the heterochromatin of Chr 17, that the Ts65Dn mark er chromosome contains a small portion of Chr 17 euchromatin, that the Chr 16 breakpoint lies between the Ncam2 and Gabpa/App genes, and that the Ts65 Dn chromosome contains > 80% of the human Chr 21 homologs. The significance of this finding is discussed in terms of the utility of this mouse model. Copyright (C) 2001 S. Karger AG, Basel.