Loss of correlations among proteins in brains of the Ts65Dn mouse model of down syndrome.
The Ts65Dn mouse model of Down syndrome (DS) is trisomic for orthologs of 88 of 161 classical protein coding genes present on human chromosome 21 (HSA21). Ts65Dn mice display learning and memory impairments and neuroanatomical, electrophysiological, and cellular abnormalities that are relevant to phenotypic features seen in DS; however, little is known about the molecular perturbations underlying the abnormalities. Here we have used reverse phase protein arrays to profile 64 proteins in the cortex, hippocampus, and cerebellum of Ts65Dn mice and littermate controls. Proteins were chosen to sample a variety of pathways and processes and include orthologs of HSA21 proteins and phosphorylation-dependent and -independent forms of non-HSA21 proteins. Protein profiles overall show remarkable stability to the effects of trisomy, with fewer than 30% of proteins altered in any brain region. However, phospho-proteins are less resistant to trisomy than their phospho-independent forms, and Ts65Dn display abnormalities in some key proteins. Importantly, we demonstrate that Ts65Dn mice have lost correlations seen in control mice among levels of functionally related proteins, including components of the MAP kinase pathway and subunits of the NMDA receptor. Loss of normal patterns of correlations may compromise molecular responses to stimulation and underlie deficits in learning and memory.
Department of Pediatrics, University of Colorado Denver , Aurora, Colorado, United States.
Md Mahiuddin
MM
Ahmed
Xiaolu
X
Sturgeon
Misoo
M
Ellison
Muriel T
MT
Davisson
Katheleen J
KJ
Gardiner
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D040081:Protein Array Analysis / Q000379:methods*; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results
D009419:Nerve Tissue Proteins; D020543:Proteome; D016194:Receptors, N-Methyl-D-Aspartate; D048049:Extracellular Signal-Regulated MAP Kinases