Segmentally trisomic Ts(1716)65Dn mice provide a postnatal model for Down syndrome. Ts65Dn mice have three copies of most of the genes on mouse Chr 16 that are homologues of human Chr 21 genes. These extra genes, along with the centromere and about 5% of proximal Chr 17 are contained in a small extra chromosome derived from a reciprocal translocation.
Neural cognitive deficits and behavioral abnormalities have been noted in Ts65Dn mice. They have spatial learning and memory defects as assessed in the Morris water maze and the radial arm maze, show developmental delay in sensorimotor milestones, and exhibit locomotor hyperactivity, lack of behavioral inhibition, and stereotypic behavior. They perform similar to controls in visual placing, balance, prehensile reflex and traction on a horizontal bar, motor coordination, swimming ability and olfaction orienting. They also show altered noradrenergic transmission in the hippocampus and cerebral cortex and degeneration of basal forebrain cholinergic neurons by 6 months of age. Trisomic females are smaller and produce fewer, smaller litters than euploid females while trisomic males are effectively sterile with hypospermia.
The precise locations of the Chr 16 and Chr 17 breakpoints are 84,351,351 bp and 9,426,822 bp, respectively. The Chr 16 segment contains about two thirds of the human Chr 21 homologues in the mouse, from mitochondrial ribosomal protein L39 (Mrpl39) gene to the distal telomere. These data were used to generate a PCR genotyping assay for Ts65Dn (Reinholdt et al., 2011), replacing the previous methods of chromosome analysis or qPCR. For comparison of segments conserved in human Chr 21 with mouse Chrs 16, 17, 10 and genetic definition of Ts65Dn, see the Human - Mouse Orthology Map. Northern and Western blotting, enzyme activity assays and reverse phase protein arrays (RPPA) demonstrate that some but not all genes in the translocation product are expressed at elevated levels in segmentally trisomic animals. RPPA shows a loss of correlation among some brain proteins (Ahmed et al., 2012). The Clcc1m1J spontaneous mutation, which causes increased sensitivity to endoplasmic reticulum stress in the cerebellum, is a homozygous strain characteristic of C3H/HeSnJ (Jia et al., 2015) so is segregating in this strain.
Please see the Down Syndrome and Cytogenetics Models Resource for more information.
