A13 Expression of FKBP51 and HAP40 protein in a congenic rat model of huntington disease

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Abstract

Background

Guo and Huang recently showed that Huntingtin protein (Htt) forms a complex with Hap40 protein. This interaction may affect structure and function of Htt. In HD patient derived fibroblasts an Hap40 upregulation was shown, leading to alterations in endosome motility underpinning a role for Hap40 in HD pathology. Likewise, a second protein of interest is FKBP51, a co-chaperone of the steroid receptor complex and regulatory protein of the HPA–axis. As HD patients often display signs of depression and anxiety including a pre-symptomatic increase in HPA–axis activity, alterations in FKBP51 expression may explain the observed symptoms.

Aims

Despite their different functions, the potential impact of Hap40 and FKBP51 on development and progression of HD appears to be of equal importance. Here we report on the expression and local distribution in brains of transgenic mouse and rat models of HD.

Methods/techniques

Hap40 and FKBP51 are studied in the congenic F344 rat model of HD and further on in BACHD and zQ175DN ki x C57BL/6N mice. The histological pattern and a potential co-localization of both proteins with Htt will be investigated with immunohistological methods. In addition, the expression on protein and mRNA level will be analysed using Western Blot and RTqPCR.

Results

For the first time, comprehensive histological analysis of Hap40 and FKBP51 in HD rat brains will be presented. So far, we established corresponding antibodies to both proteins for immunohistological investigations. Specific primers for FKBP51 and Hap40 were generated and are currently tested for RTqPCR. In addition, Western Blots will be performed on selected brain regions. Results will be presented in further detail on the EHDN Meeting.

Conclusion

The expression pattern of Htt-stabilizing protein Hap40 and of stress-regulatory protein FKBP51 is investigated in the F344 HD model to detect possible alterations that contribute to disease pathology.

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