An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes.
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.
O'Doherty
Aideen
A
Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
Ruf
Sandra
S
Mulligan
Claire
C
Hildreth
Victoria
V
Errington
Mick L
ML
Cooke
Sam
S
Sesay
Abdul
A
Modino
Sonie
S
Vanes
Lesley
L
Hernandez
Diana
D
Linehan
Jacqueline M
JM
Sharpe
Paul T
PT
Brandner
Sebastian
S
Bliss
Timothy V P
TV
Henderson
Deborah J
DJ
Nizetic
Dean
D
Tybulewicz
Victor L J
VL
Fisher
Elizabeth M C
EM
D000782:Aneuploidy; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D002452:Cell Count; D002460:Cell Line; D002678:Chimera; D002891:Chromosomes, Human, Pair 21; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics / Q000503:physiopathology; D004622:Embryo, Mammalian / Q000166:cytology; D005147:Facial Bones / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005818:Genetic Engineering; D005819:Genetic Markers; D006330:Heart Defects, Congenital / Q000196:embryology; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D017774:Long-Term Potentiation; D008213:Lymphocyte Activation; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012886:Skull / Q000473:pathology; D013234:Stem Cells; D009435:Synaptic Transmission; D013601:T-Lymphocytes / Q000276:immunology
D005819:Genetic Markers