Species: Mouse
Modification: Other
Disease Relevance: Alzheimer's Disease, Down's Syndrome
Strain Name: B6EiC3Sn a/A-Ts(17¹⁶)65Dn/J
Genetic Background: DBA/2J
Availability: The Jackson Lab: Stock# 001924; Live. The CRO PsychoGenics offers research services with this line.

Summary

This well-characterized model of Down's syndrome develops elevated APP but lacks appreciable β-amyloid pathology. The mice are aneuploid and carry the translocation chromosome, Mmu17¹⁶ (17¹⁶), as a freely segregating, supernumerary chromosome. The 17¹⁶ chromosome carries approximately 13.4 Mb of distal chromosome 16, from Mrpl39 to Zfp295, fused with about 10 Mb of chromosome 17, just proximal to the centromere. The precise locations of the chromosome 16 and chromosome 17 breakpoints are 84,351,351 bp and 9,426,822 bp, respectively (Reinholdt et al., 2011).

These mice are affected by reduced birthweight, muscular trembling, male sterility, and an abnormal facial appearance (Davisson et al., 1990). From a young age, many deficits in behavior and cognition have also been observed. They have spatial learning and memory deficits as assessed by 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.

The brains of Ts65Dn mice are grossly normal. Neuropathologically they show age-dependent cholinergic neurodegeneration in the basal forebrain between six and twelve months of age (Holtzman et al., 1996). They also have a reduction in nerve growth factor (NGF) in the basal forebrain at this time (Hunter et al., 2003). Alterations in synaptic plasticity and adult neurogenesis have also been reported. They do not have evidence of β-amyloid pathology (Holtzman et al., 1996) despite age-related elevation of APP and Aβ in the hippocampus (Hunter et al., 2003).

These mice are on a genetic background that leads to blindness in about 25 percent of progeny due to the retinal degeneration allele Pde6b^rd1. Mice that are homozygous for the rd1 allele are affected. An alternative strain is available (The Jackson Lab Stock# 005252) with a virtually identical genetic background except that it is wild-type for Pde6b^rd1. Only subtle phenotypic differences have been observed between the two strains (Costa et al., 2010).

Modification Details

Cesium irradiation produced a reciprocal translocation of chromosomes 16 and 17, creating a freely segregating, supernumerary chromosome Mmu1716 (1716).

Availability

These mice are available as a live stock through The Jackson Lab: Stock# 001924. The contract research organization PsychoGenics offers research services with this line.

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References

Paper Citations

1. Reinholdt LG, Ding Y, Gilbert GJ, Gilbert GT, Czechanski A, Solzak JP, Roper RJ, Johnson MT, Donahue LR, Lutz C, Davisson MT. Molecular characterization of the translocation breakpoints in the Down syndrome mouse model Ts65Dn. Mamm Genome. 2011 Dec;22(11-12):685-91. Epub 2011 Sep 28 PubMed.
2. Davisson MT, Schmidt C, Akeson EC. Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome. Prog Clin Biol Res. 1990;360:263-80. PubMed.
3. Holtzman DM, Santucci D, Kilbridge J, Chua-Couzens J, Fontana DJ, Daniels SE, Johnson RM, Chen K, Sun Y, Carlson E, Alleva E, Epstein CJ, Mobley WC. Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13333-8. PubMed.
4. Hunter CL, Isacson O, Nelson M, Bimonte-Nelson H, Seo H, Lin L, Ford K, Kindy MS, Granholm AC. Regional alterations in amyloid precursor protein and nerve growth factor across age in a mouse model of Down's syndrome. Neurosci Res. 2003 Apr;45(4):437-45. PubMed.
5. Costa AC, Stasko MR, Schmidt C, Davisson MT. Behavioral validation of the Ts65Dn mouse model for Down syndrome of a genetic background free of the retinal degeneration mutation Pde6b(rd1). Behav Brain Res. 2010 Jan 5;206(1):52-62. Epub 2009 Aug 29 PubMed.

External Citations

1. The Jackson Lab Stock# 005252
2. The Jackson Lab: Stock# 001924
3. PsychoGenics
4. The Jackson Lab: Stock# 001924

Further Reading