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PMID: 16179473 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Science (New York, N.Y.) ·Vol. 309 ·No. 5743 ·2005-09-23 ·Pages 2033-7

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 TV, Henderson DJ, Nizetic D, Tybulewicz VL, Fisher EM

Abstract

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, Tc1, 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 aneuploidies.

MeSH Terms
Aneuploidy Animals Behavior, Animal Brain/pathology Cell Count Cell Line Chimera Chromosomes, Human, Pair 21 Disease Models, Animal Down Syndrome/genetics,physiopathology Embryo, Mammalian/cytology Facial Bones/pathology Female Gene Expression Genetic Engineering Genetic Markers Heart Defects, Congenital/embryology Hippocampus/physiopathology Humans Long-Term Potentiation Lymphocyte Activation Male Maze Learning Memory Mice Mice, Inbred Strains Mice, Transgenic Neurons/cytology Oligonucleotide Array Sequence Analysis Phenotype Skull/pathology Stem Cells Synaptic Transmission T-Lymphocytes/immunology
Chemicals
Genetic Markers
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
O'Doherty Aideen
Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Ruf Sandra
Mulligan Claire
Hildreth Victoria
Errington Mick L
Cooke Sam
Sesay Abdul
Modino Sonie
Vanes Lesley
Hernandez Diana
Linehan Jacqueline M
Sharpe Paul T
Brandner Sebastian
Bliss Timothy V P
Henderson Deborah J
Nizetic Dean
Tybulewicz Victor L J
Fisher Elizabeth M C
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1114535
Published
2005-09-23
Pages
2033-7
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC1378183
Subset
IM
Grants
Wellcome Trust · 076700 · United Kingdom
Medical Research Council · MC_U117512674 · United Kingdom
Corrections
CommentIn
PMID: 16179439
External Links
PubMed source DOI: 10.1126/science.1114535 PMC Full Text View journal details
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