The use of mouse models to understand and improve cognitive deficits in Down syndrome - PubMed (original) (raw)

Review

The use of mouse models to understand and improve cognitive deficits in Down syndrome

Ishita Das et al. Dis Model Mech. 2011 Sep.

Abstract

Remarkable advances have been made in recent years towards therapeutics for cognitive impairment in individuals with Down syndrome (DS) by using mouse models. In this review, we briefly describe the phenotypes of mouse models that represent outcome targets for drug testing, the behavioral tests used to assess impairments in cognition and the known mechanisms of action of several drugs that are being used in preclinical studies or are likely to be tested in clinical trials. Overlaps in the distribution of targets and in the pathways that are affected by these diverse drugs in the trisomic brain suggest new avenues for DS research and drug development.

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Figures

Fig. 1.

Fig. 1.

Mouse models of Down syndrome (DS). Mouse orthologous regions to Hsa21 that are present on Mmu16, Mmu17 and Mmu10 are represented above and below Hsa21. The flanking genes found at the boundaries of the triplicated region in each model are depicted in italics; the approximate number of Hsa21 orthologous genes is shown in parentheses (not yet reported for the Tc1 strain). Mmu16 has the largest region of homology with Hsa21, and the Ts1Yey mouse [Dp(16Lipi-Zfp295)1Yey] contains the entire homologous region in trisomy. Ts65Dn, Ts1Cje and Ts1Rhr mice are segmental trisomies containing partial segments of Mmu16. The more recently developed segmental trisomic mouse strains Ts1Yah and Ts3Yey [Dp(17Abcg1-Rrp1b)1Yey] have three copies of the Hsa21-orthologous region of Mmu17, whereas Ts2Yey mice [Dp(10Prmt2-Pdxk)1Yey] and Ts3Yah mice duplicate the region on Mmu10. Tc1 is a transchromosomic mouse model bearing a mostly intact copy of Hsa21, producing trisomy for about 80% of the genes on that chromosome. Ts2Yey is the official alternate name for Dp(10Prmt2-Pdxk)1Yey on the MGI database, but has been referred to as Ts1Yey in print (Yu et al., 2010b). Combining the triplicated regions of Ts1Yey, Ts2Yey and Ts3Yey produces the triple trisomy model that is trisomic for all mouse orthologs of Hsa21 genes.

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