title: An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes.
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.
authors.affiliation: Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Aideen
authors.initials: A
authors.lastname: O'Doherty
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruf
authors.forename: Claire
authors.initials: C
authors.lastname: Mulligan
authors.forename: Victoria
authors.initials: V
authors.lastname: Hildreth
authors.forename: Mick L
authors.initials: ML
authors.lastname: Errington
authors.forename: Sam
authors.initials: S
authors.lastname: Cooke
authors.forename: Abdul
authors.initials: A
authors.lastname: Sesay
authors.forename: Sonie
authors.initials: S
authors.lastname: Modino
authors.forename: Lesley
authors.initials: L
authors.lastname: Vanes
authors.forename: Diana
authors.initials: D
authors.lastname: Hernandez
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Linehan
authors.forename: Paul T
authors.initials: PT
authors.lastname: Sharpe
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandner
authors.forename: Timothy V P
authors.initials: TV
authors.lastname: Bliss
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Henderson
authors.forename: Dean
authors.initials: D
authors.lastname: Nizetic
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
mesh_terms: 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
chemical_list: D005819:Genetic Markers