Quantitative proteomics characterization of a mouse embryonic stem cell model of Down syndrome

Topic: Brain proteins, microglia and lab models

Down syndrome, caused by the trisomy of chromosome 21, is a complex condition characterized by a number of phenotypic features, including reduced neuron number and synaptic plasticity, early Alzheimer disease-like neurodegeneration, craniofacial dysmorphia, heart development defects, increased incidence of childhood leukemia, and powerful suppression of the incidence of most solid tumors. Mouse models replicate a number of these phenotypes. The Tc1 Down syndrome model was constructed by introducing a single supernumerary human chromosome 21 into a mouse embryonic stem cell, and it reproduces a large number of Down syndrome phenotypes including heart development defects. However, little is still known about the developmental onset of the trisomy 21-induced mechanisms behind these phenotypes or the proteins that are responsible for them. This study determined the proteomic differences that are present in undifferentiated embryonic stem cells and are caused by an additional human chromosome 21. A total of 1661 proteins were identified using two-dimensional liquid chromatography followed by tandem mass spectrometry from whole embryonic stem cell lysates. Using isobaric tags for relative and absolute quantification, we found 52 proteins that differed in expression by greater than two standard deviations from the mean when an extra human chromosome 21 was present. Of these, at least 11 have a possible functional association with a Down syndrome phenotype or a human chromosome 21-encoded gene. This study also showed that quantitative protein expression differences in embryonic stem cells can persist to adult mouse as well as reproduce in human Down syndrome fetal tissue. This indicates that changes that are determined in embryonic stem cells of Down syndrome could potentially identify proteins that are involved in phenotypes of Down syndrome, and it shows that these cell lines can be used for the purpose of studying these pathomechanisms.

Key findings

• Using isobaric tags for relative and absolute quantification, we found 52 proteins that differed in expression by greater than two standard deviations from the mean when an extra human chromosome 21 was present.
• This study also showed that quantitative protein expression differences in embryonic stem cells can persist to adult mouse as well as reproduce in human Down syndrome fetal tissue.
• This indicates that changes that are determined in embryonic stem cells of Down syndrome could potentially identify proteins that are involved in phenotypes of Down syndrome, and it shows that these cell lines can be used for the purpose of studying these pathomechanisms.

Why it matters

In mouse embryonic stem cells with an extra human chromosome 21, this study found 52 proteins that differed in expression, and some of these differences persisted into adult mice and appeared in human Down syndrome fetal tissue. This is early laboratory work and does not by itself show any treatment or prevention for Alzheimer's disease.

Study details

• Participants1,661
• Evidence strengthLow

Read the original

• DOI: 10.1074/mcp.m800256-mcp200
• PubMed: 19001410
• Original source →
• Free full text: Molecular & Cellular Proteomics →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{wang2009-19001410,
  author  = {Wang, Y. and Mulligan, C. and Denyer, G. and Delom, F. and Dagna-Bricarelli, F. and Tybulewicz, V. L. and Fisher, E. M. and Griffiths, W. J. and others},
  title   = {{Quantitative proteomics characterization of a mouse embryonic stem cell model of Down syndrome}},
  journal = {Molecular \& cellular proteomics : MCP},
  year    = {2009},
  doi     = {10.1074/mcp.m800256-mcp200},
  pmid    = {19001410},
  url     = {https://doi.org/10.1074/mcp.m800256-mcp200}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study Lancet (London, England) · 2002-03-01 · usefulness score 61/100 · Getting a diagnosis
• A mouse model for Down syndrome exhibits learning and behaviour deficits Nature genetics · 1995-10-01 · usefulness score 54/100 · Down syndrome and Alzheimer's
• Proteomic signatures and aberrations of mouse embryonic stem cells containing a single human chromosome 21 in neuronal differentiation: an in vitro model of Down syndrome Neuroscience · 2004-01-01 · usefulness score 37/100 · Down syndrome and Alzheimer's
• An additional human chromosome 21 causes suppression of neural fate of pluripotent mouse embryonic stem cells in a teratoma model BMC developmental biology · 2007-11-29 · usefulness score 37/100 · Biomarkers

Later studies that cite this one

1 study in the alzhub library lists this one in its references.

• Disturbance of redox homeostasis in Down Syndrome: Role of iron dysmetabolism Free radical biology & medicine · 2017-07-10 · usefulness score 42/100 · Down syndrome and Alzheimer's

Related studies in Down syndrome and Alzheimer's

• Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells The Journal of biological chemistry · 2009-06-19 · usefulness score 42/100
• A human stem cell model of early Alzheimer's disease pathology in Down syndrome Science translational medicine · 2012-02-15 · usefulness score 36/100
• Molecular characterization of the translocation breakpoints in the Down syndrome mouse model Ts65Dn Mammalian genome : official journal of the International Mammalian Genome Society · 2011-09-28 · usefulness score 36/100
• Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2 Genes, brain, and behavior · 2009-09-22 · usefulness score 34/100
• Cerebral cortical astroglia from the trisomy 16 mouse, a model for down syndrome, produce neuronal cholinergic deficits in cell culture Proceedings of the National Academy of Sciences of the United States of America · 1997-11-01 · usefulness score 38/100
• Lens defects and age-related fiber cell degeneration in a mouse model of increased AbetaPP gene dosage in Down syndrome The American journal of pathology · 2002-12-01 · usefulness score 34/100

Also tagged “down”

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• Synaptic actin stabilization protein loss in Down syndrome and Alzheimer disease Brain pathology (Zurich, Switzerland) · 2019-09-08 · usefulness score 38/100 · Down syndrome and Alzheimer's
• Elimination of amyloid precursor protein in senile plaques in the brain of a patient with Alzheimer-type dementia and Down syndrome Brain & development · 2018-08-04 · usefulness score 33/100 · Down syndrome and Alzheimer's
• Neuropsychiatric and behavioral aspects of trisomy 21 Current psychiatry reports · 2007-04-01 · usefulness score 37/100 · Down syndrome and Alzheimer's

Similar studies

• An investigation of the molecular mechanisms engaged before and after the development of Alzheimer disease neuropathology in Down syndrome: a proteomics approach 2014 · Down syndrome and Alzheimer's
• Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome 1996 · Down syndrome and Alzheimer's
• Functional genomics of the Down syndrome 2001 · Down syndrome and Alzheimer's
• Genetic analysis of Down syndrome facilitated by mouse chromosome engineering 2012 · Down syndrome and Alzheimer's
• Protein expression in Down syndrome brain 2001 · Down syndrome and Alzheimer's
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More on Down syndrome and Alzheimer's

• A review that covers this ground Segmental trisomy as a mouse model for Down syndrome Progress in clinical and biological research · 1993-01-01 · usefulness score 41/100
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• Newest in this subject Memory and Plasma pTau217 Refine Prognosis in Down Syndrome Annals of neurology · 2026-10-02 · Peer-reviewed · usefulness score 47/100

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