Immunohistochemical and behavioral assessment of FKBP51‐Hsp90 interaction‐deficient mouse crossed with Alzheimer tau transgenic Tg4510 mice

Abstract

AbstractBackgroundFK506‐binding protein 51 kDa (FKBP51) is a heat shock protein 90 (Hsp90) associated co‐chaperone which has recently emerged as a possible Alzheimer disease (AD) therapeutic target involved in tau metabolism. Increased expression of FKBP51 was found in brains of aged mice and AD patients and overexpression of FKBP51 in mice impairs cognitive function in vivo. To elucidate the role of FKBP51‐Hsp90 complex in tau biology in vivo we have crossed well characterized tau transgenic Tg4510 mice with our novel FKBP51‐Hsp90 interaction‐deficient mice (Fkbp5TPRmut).Methods• Using PCR amplification, we have confirmed correct genotype of crossings.• Immunohistochemical staining of brains of 4 months‐old animals with total tau and phospho‐tau antibodies.• Behavior assessment of cognition and memory using open field, novel object recognition, Y‐maze, and fear conditioning tests.Results• Successful crossings between Fkbp5TPRmut and Tg4510 mice have been obtained• We have confirmed phospho‐tau expression in the cortex and hippocampus of 4 months‐old transgene‐expressing animals (positive controls).• Immunohistochemical assessment of phospho‐tau expression in the cortex and hippocampus of wild‐type and Fkbp5TPRmut x Tg4510 crossings is ongoing.• Behavioral assessment of Wt x Tg4510 and Fkbp5TPRmut x Tg4510 crossings is ongoing.Conclusion• Fkbp5TPRmut crossings with Tg4510 mice do not display harmful phenotype.• Behavioral and immunohistochemical evaluation experiments are ongoing and will soon be completed.