Updated 16 March 2009

General Information

Transgene: Cesium irradiation produced a reciprocal translocation, T65Dn, in which the distal end of mouse Chr 16 (homologous to human Chr 21) is translocated to Chr 17, this extra chromosome contains genes from App to Mx/1.

Mutation: Triple copy of mouse APP

Promoter:  murine Thy-1

Mouse strain: B6EiC3Sn a/A-Ts(17¹⁶)65Dn N=37

Phenotype

Neuropathological analysis

DAPP mRNA and protein from the cerebral cortex are elevated by 2.5- and 2-fold, respectively, at E15. Increased levels of APP in the striatum by 6-8 months of age, and in the hippocampus and parietal cortex by 13-16 months of age. Mice also showed decline in NGF levels in basal forebrain and hippocampal with age (Hunter, 2003). At 6 months mice exhibit higher levels of β-amyloid in the hippocampus. Mice undergo decline in cholinergic phenotype and cognitive deterioration starting at 6-8 months.

Behavioral

Reduced birth weight, postnatal developmental delay, muscular trembling, male sterility, abnormal facies and reduced learning ability, which suggest dysfunction of the hippocampus.

Availability

Licensing/academic distribution contact information:

The Jackson Lab , Stock #001924. For recipient’s research only, not to be sold to third parties for breeding or any other use.

Patents: None

References

Primary:

M.T. Davisson, C. Schmidt and E.C. Akeson, Segmental trisomy of murine chromosome 16: a new model system for studying Down syndrome. Prog. Clin. Biol. Res. 360:263-280, 1990. Abstract

Associated:

Delcroix JD, Valletta J, Wu C, Howe CL, Lai CF, Cooper JD, Belichenko PV, Salehi A, Mobley WC. Trafficking the NGF signal: implications for normal and degenerating neurons. Prog Brain Res. 146:3-23, 2004. Abstract

Hunter CL, Bimonte-Nelson HA, Nelson M, Eckman CB, Granholm AC. Behavioral and neurobiological markers of Alzheimer's disease in TS65Dn mice: effects of estrogen. Neurobiol Aging 25:873-884, 2004. Abstract

Granholm AC, Sanders L, Seo H, Lin L, Ford K, Isacson O. Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome. Hippocampus. 2003 Jan 1 ; 13(8):905-14. Abstract

Cataldo AM, Petanceska S, Peterhoff CM, Terio NB, Epstein CJ, Villar A, Carlson EJ, Staufenbiel M, Nixon RA. App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16-mouse model of down syndrome. J Neurosci. 23(17): 6788-92, 2003. Abstract

Granholm AC, Sanders L, Seo H, Lin L, Ford K, Isacson O. Estrogen alters amyloid precursor protein as well as dendritic and cholinergic markers in a mouse model of Down syndrome. Hippocampus 13(8):905-14, 2003. Abstract

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. 45(4): 437-45, 2003. Abstract

Hunter CL, Bimonte HA, Granholm AC. Behavioral comparison of 4 and 6 month-old Ts65Dn mice: age-related impairments in working and reference memory. Behav Brain Res. 138(2):121-31, 2003. Abstract

Bimonte-Nelson HA, Hunter CL, Nelson ME, Granholm AC. Frontal cortex BDNF levels correlate with working memory in an animal model of Down syndrome. Behav Brain Res. 139(1-2):47-57, 2003. Abstract

Frederikse PH, Ren XO. Lens defects and age-related fiber cell degeneration in a mouse model of increased AbetaPP gene dosage in Down syndrome. Am J Pathol. 161(6):1985-90, 2002. Abstract

Busciglio J, Pelsman A, Wong C, Pigino G, Yuan M, Mori H, Yankner BA. Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron 33(5):677-88, 2002. Abstract

Hyde LA, Crnic LS. Age-related deficits in context discrimination learning in Ts65Dn mice that model Down syndrome and Alzheimer's disease. Behav Neurosci. 115(6): 1239-46, 2001. Abstract

Cooper JD, Salehi A, Delcroix JD, Howe CL, Belichenko PV, Chua-Couzens J, Kilbridge JF, Carlson EJ, Epstein CJ, Mobley WC. Failed retrograde transport of NGF in a mouse model of Down's syndrome: reversal of cholinergic neurodegenerative phenotypes following NGF infusion. Proc Natl Acad Sci U S A. 98(18):10439-44, 2001. Abstract

Sago H, Carlson EJ, Smith DJ, Kilbridge J, Rubin EM, Mobley WC, Epstein CJ, Huang TT. Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities. Proc Natl Acad Sci U S A. 95(11):6256-61, 1998. Abstract

A.M. Insausti, M. Megias, D. Crespo, L.M. Cruz-Orive, M. Dierssen, I.F. Vallina, R. Insausti, J. Florez and T.F. Vallina. Hippocampal volume and neuronal number in Ts65Dn mice: a murine model of Down syndrome [published erratum appears in Neurosci. Lett. 258(3) (1998) 190]. Neurosci. Lett. 253: 175-178, 1998. Abstract

M. Megias, R. Verduga, M. Dierssen, J. Florez, R. Insausti and D. Crespo. Cholinergic, serotonergic and catecholaminergic neurons are not affected in Ts65Dn mice. Neuroreport 8: 3475-3478, 1997. Abstract

D.M. Holtzman, D. Santucci, J. Kilbridge, J. Chua-Couzens, D.J. Fontana, S.E. Daniels, R.M. Johnson, K. Chen, Y. Sun, E. Carlson, E. Alleva, C.J. Epstein and W.C. Mobley. Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. Proc. Natl. Acad. Sci. USA 93:13333-13338, 1996. Abstract

Holtzman DM, Kilbridge J, Chen KS, Rabin J, Luche R, Carlson E, Epstein CJ, Mobley WC. Preliminary characterization of the central nervous system in partial trisomy 16 mice. Prog Clin Biol Res. 393:227-40. Review, 1995. Abstract

R.H. Reeves, N.G. Irving, T.H. Moran, A. Wohn, C. Kitt, S.S. Sisodia, C. Schmidt, R.T. Bronson and M.T. Davisson. A mouse model for Down syndrome exhibits learning and behaviour deficits. Nat. Genet. 11:177-184, 1995. Abstract

Higgins LS, Holtzman DM, Rabin J, Mobley WC, Cordell B. Transgenic mouse brain histopathology resembles early Alzheimer's disease. Ann Neurol. 35(5):598-607, 1994. Abstract

Holtzman DM, Li Y, Chen K, Gage FH, Epstein CJ, Mobley WC. Nerve growth factor reverses neuronal atrophy in a Down syndrome model of age-related neurodegeneration. Neurology. 43(12):2668-73, 1993. Abstract

Holtzman DM, Bayney RM, Li YW, Khosrovi H, Berger CN, Epstein CJ, Mobley WC. Dysregulation of gene expression in mouse trisomy 16, an animal model of Down syndrome.EMBO J. 11(2):619-27, 1992. Abstract

Holtzman DM, Li YW, DeArmond SJ, McKinley MP, Gage FH, Epstein CJ, Mobley WC. Mouse model of neurodegeneration: atrophy of basal forebrain cholinergic neurons in trisomy 16 transplants. Proc Natl Acad Sci U S A. 89(4):1383-7, 1992. Abstract