Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse lines: relevance for modeling Down syndrome.
Identification of the translocation breakpoints in the Ts65Dn and Ts1Cje mouse lines: relevance for modeling Down syndrome.
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识别TS65DN和TS1CJE鼠标线中的易位断点：与唐氏综合症建模的相关性。
DOI：
10.1007/s00335-011-9356-0
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发表时间：
2011-12
期刊：
影响因子：
2.5
通讯作者：
Herault, Yann
中科院分区：
文献类型：
--
作者：
Duchon, Arnaud;Raveau, Matthieu;Chevalier, Claire;Nalesso, Valerie;Sharp, Andrew J.;Herault, Yann
唐氏综合症（DS）是最常见的导致智力残疾的遗传性疾病，由人类21号染色体的三个副本引起。小鼠模型被广泛用于更好地了解DS的病理生理学或测试新的治疗方法。最古老和最广泛使用的小鼠模型是三体Ts65Dn和Ts1Cje小鼠。他们表现出与DS人相似的缺陷，如行为和认知或神经元异常。Ts65Dn模型目前用于候选药物的进一步治疗评估。在这两种模型中，三体性是由相互染色体易位诱导的，未进一步表征。使用比较基因组学方法，我们已经能够精确地定位在这两个模型中的易位断点，我们利用这一发现，以获得一个新的和更有效的Ts65Dn基因分型策略。此外，我们发现，易位引入额外的非整倍体在这两个模型中，与单体的7个基因在小鼠染色体12的最端粒部分的Ts1Cje和小鼠染色体17上的Ts65Dn的60个着丝粒基因的三体。最后，我们在这里报告的新发现的非整倍体基因在Ts65Dn心脏的过度表达，我们讨论了它们的潜在影响的DS模型的有效性。
Down syndrome (DS) is the most frequent genetic disorder leading to intellectual disabilities and is caused by three copies of human chromosome 21. Mouse models are widely used to better understand the physiopathology in DS or to test new therapeutic approaches. The older and the most widely used mouse models are the trisomic Ts65Dn and the Ts1Cje mice. They display deficits similar to those observed in DS people, such as those in behavior and cognition or in neuronal abnormalities. The Ts65Dn model is currently used for further therapeutic assessment of candidate drugs. In both models, the trisomy was induced by reciprocal chromosomal translocations that were not further characterized. Using a comparative genomic approach, we have been able to locate precisely the translocation breakpoint in these two models and we took advantage of this finding to derive a new and more efficient Ts65Dn genotyping strategy. Furthermore, we found that the translocations introduce additional aneuploidy in both models, with a monosomy of seven genes in the most telomeric part of mouse chromosome 12 in the Ts1Cje and a trisomy of 60 centromeric genes on mouse chromosome 17 in the Ts65Dn. Finally, we report here the overexpression of the newly found aneuploid genes in the Ts65Dn heart and we discuss their potential impact on the validity of the DS model.
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影响因子：
2.5
作者：
Belichenko, PV;Masliah, E;Mobley, WC
通讯作者：
Mobley, WC
DOI：
10.1177/0269881111405366
发表时间：
2011-08
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Braudeau J;Delatour B;Duchon A;Pereira PL;Dauphinot L;de Chaumont F;Olivo-Marin JC;Dodd RH;Hérault Y;Potier MC
通讯作者：
Potier MC
影响因子：
3.3
作者：
Duchon, Arnaud;Besson, Vanessa;Herault, Yann
通讯作者：
Herault, Yann
影响因子：
2.5
作者：
Belichenko, Pavel V.;Klescrevnikov, Alexander M.;Mobley, William C.
通讯作者：
Mobley, William C.
影响因子：
2
作者：
Hill, Cheryl A.;Sussan, Thomas E.;Reeves, Roger H.;Richtsmeier, Joan T.
通讯作者：
Richtsmeier, Joan T.