|SCHMITZ, MATRHAIS - Georg August University|
|Silva, Christopher - Chris|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 3/30/2015
Publication Date: 5/1/2015
Publication URL: http://www.tandfonline.com/doi/pdf/10.1080/19336896.2015.1033248
Citation: Schmitz, M., Silva, C.J. 2015. PrP0\0 mice show behavioral abnormalities that suggest PrPC has a role in maintaining the cytoskeleton.. Meeting Abstract. Prion (Supplement 1) 9: S73-S74..
Interpretive Summary: Certain transmissible brain diseases in animals involve a highly conserved and important brain protein, PrPC. We want to better understand the natural purpose of this protein. In order to do this we compared the observed the behaviors of ordinary mice that are able to make PrPC and transgenic mice that are not able to make PrPC. The transgenic mice built worse nests, had poorer memories, and learned slower than the ordinary mice. Next, we wanted to compare proteins other than PrPC from normal mice and transgenic mice to see if there were differences. We found more of four proteins in older normal mice but not in older transgenic mice. Another five proteins were found in different amounts in cells from normal mice than in transgenic mice. All of these proteins were involved in organizing the scaffolding that gives these cells their structure. We now understand that PrPC is involved in maintaining the structure of brain cells and in minimizing age-dependent changes in the brain.
Technical Abstract: Background/Introduction. PrPC is highly conserved among mammals, but its natural function is unclear. Prnp ablated mice (PrP0/0) appear to develop normally and are able to reproduce. These observations seem to indicate that the gene is not essential for viability, in spite of it being highly conserved. Materials and Methods. A variety of models were used to better understand the physiological role of PrPC. Wild type (WT) and PrP0/0 mice were subjected to a series of standard behavioral tests to detect phenotypic differences. Tissues from these mice were studied at the physiological level. Biochemical differences in mouse derived tissues were examined by mass spectrometry. Results and Conclusions. PrP0/0, but not WT, mice showed a substantially reduced ability to build nests. Age-dependent behavioral deficits in memory performance, associative learning, and basal anxiety were also observed in PrP0/0 mice. WT, but not PrP0/0, mice showed increases in four neurofilament (NF) proteins as they aged. Five other proteins were found to be differentially abundant in older (18 month) WT but not in PrP0/0 mice. NF-H phosphorylation was reduced in both PrP0/0 mouse and cell models. PrPC ablation was associated with the expression of Fyn and phospho-Fyn, a potential regulator for NF phosphorylation. The number of '-tubulin III-positive neurons in the hippocampus was diminished in PrP0/0 mice relative to WT mice. These data indicate that PrPC plays an important role in cytoskeletal organization, brain function, and age-related neuroprotection. Our work represents the first direct biochemical link between these proteins and the observed behavioral phenotypes.