Article

Molecular characterization of the translocation breakpoints in the Down syndrome mouse model Ts65Dn.Mamm

The Jackson Laboratory, Genetic Resource Science, ME, 04609, USA.
Mammalian Genome (Impact Factor: 3.07). 09/2011; 22(11-12):685-91. DOI: 10.1007/s00335-011-9357-z
Source: PubMed

ABSTRACT

Ts65Dn is a mouse model of Down syndrome: a syndrome that results from chromosome (Chr) 21 trisomy and is associated with congenital defects, cognitive impairment, and ultimately Alzheimer's disease. Ts65Dn mice have segmental trisomy for distal mouse Chr 16, a region sharing conserved synteny with human Chr 21. As a result, this strain harbors three copies of over half of the human Chr 21 orthologs. The trisomic segment of Chr 16 is present as a translocation chromosome (Mmu17(16)), with breakpoints that have not been defined previously. To molecularly characterize the Chrs 16 and 17 breakpoints on the translocation chromosome in Ts65Dn mice, we used a selective enrichment and high-throughput paired-end sequencing approach. Analysis of paired-end reads flanking the Chr 16, Chr 17 junction on Mmu17(16) and de novo assembly of the reads directly spanning the junction provided the precise locations of the Chrs 16 and 17 breakpoints at 84,351,351 and 9,426,822 bp, respectively. These data provide the basis for low-cost, highly efficient genotyping of Ts65Dn mice. More importantly, these data provide, for the first time, complete characterization of gene dosage in Ts65Dn mice.

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Available from: Anne Czechanski, Mar 23, 2015
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    • "Animals Ts65Dn (Jackson Laboratories, Bar Harbor ME) and control diploid littermates were bred to have the mixed genetic background C57BL/6JEi9C3H/HeSnJ as used in our previous studies (Siarey et al. 1997; Harashima et al. 2006b; Best et al. 2012). PCR genotyping was performed on genomic DNA extracted from tail tips according to the methods described in Lorenzi et al. (2010) or Reinholdt et al. (2011. Mice were maintained under a 12-h light/dark cycle and fed standard laboratory food (following NIH guidelines). "
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    • "mice were genotyped by PCR (Fotaki et al., 2002; Guedj et al., 2012) and Ts65Dn mice by PCR (Reinholdt et al., 2011) or by quantitative PCR (http://www.jax.org/cyto/quanpcr.html). All the experimental procedures were carried out in accordance with the European Union guidelines (Directive 2010/63/EU) and the followed protocols were approved by the ethics committee of the Parc Científic de Barcelona (PCB). "
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    • "In particular, they noted that APP transgenic mice show consistent sleep disturbances in multiple studies (Colas et al. 2004). However, recent findings in Tc1 mice that the final coding exon of APP is rearranged with no human APP protein detectable would argue that loci other than APP contribute to the sleep phenotypes in Down syndrome mutant models (Reinholdt et al. 2011). Although not fully investigated in Tc1 mice, data from human studies and from other mouse models would suggest that rest/activity and rhythm disturbances may arise as a consequence of either generalized synaptic deficits or disturbances in particular brain circuitries. "
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