Molecular Mechanisms Controlling Phosphodiesterase 11A4 (Pde11A4) Protein Expression And Subcellular Localization In Balb/Cj Vs. C57Bl/6J Mice

Phosphodiesterases (PDE) are enzymes responsible for terminating cyclic nucleotide signaling. Neuropsychiatric patients such as those with Alzheimer’s disease show a dysregulation of cyclic nucleotides as well as a dysfunction in the ventral hippocampus (VHIPP) region of the brain which is responsible for social behavior and memory. Phosphodiesterase 11A4 (PDE11A4) occurs primarily in the VHIPP. Previous research has shown that BALB/cJ mice show higher levels of PDE11A4 protein expression in both dorsal hippocampus (DHIPP) and VHIPP as well as more expression in the membrane relative to C57BL/6J mice. The aim of this research is to a) determine the mRNA expression of PDE11A4 in these two mice strains by in situ hybridization of the hippocampus using a PDE11A4 probe. Results indicate greater PDE11A4 mRNA expression levels in BALB/cJ mice compared to C57BL/6J only in the DHIPP unlike previous research that found differences in both the DHIPP and VHIPP; b) to determine the effects of a coding difference at Residue 499 on subcellular localization by microscopy of HEK293T cells and protein quantification of COS 1 cells. Microscopy analysis and Western Blot results show that BALB/cJ mice have a higher membrane fraction of PDE11A4 relative to C57BL/6J mice, similar to previous research that showed a higher membrane fraction in BALB/cJ mice