An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes

被引：322

作者：

O'Doherty, A

Ruf, S

Mulligan, C

Hildreth, V

Errington, ML

Cooke, S

Sesay, A

Modino, S

Vanes, L

Hernandez, D

Linehan, JM

Sharpe, PT

Brandner, S

Bliss, TVP

Henderson, DJ

Nizetic, D

Tybulewicz, VLJ

Fisher, EMC

机构：

[1] Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England

[2] Inst Neurol, MRC, Prion Unit, London WC1N 3BG, England

[3] Natl Inst Med Res, London NW7 1AA, England

[4] Queen Marys Sch Med, Barts & London, Inst Cell & Mol Sci, Ctr Haematol, London E1 2AT, England

[5] Newcastle Univ, Inst Human Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[6] Guys Hosp, Univ London Kings Coll, Dept Craniofacial Dev, London SE1 9RT, England

来源：

SCIENCE | 2005年 / 309卷 / 5743期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1126/science.1114535

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Aneuploidies are common chromosomal defects that result in growth and developmental deficits and high levels of lethality in humans'. To gain insight into the biology of aneuploidies, we manipulated mouse embryonic stem cells and generated a trans-species aneuploid mouse line that stably transmits a freely segregating, almost complete human chromosome 21 (Hsa21). This "'transchromosomic" mouse line, TO, is a model of trisomy 21, which manifests as Down syndrome (DS) in humans, and has phenotypic alterations in behavior, synaptic plasticity, cerebellar neuronal number, heart development, and mandible size that relate to human DS. Transchromosomic mouse lines such as Tc1 may represent useful genetic tools for dissecting other human aneupioidies.

引用

页码：2033 / 2037

页数：5

共 40 条

[1] Chromosome 21 and Down syndrome: From genomics to pathophysiology [J].