Abnormalities in neuronal and glial composition of hippocampal dentate gyrus in GNB5 heterozygous mice
Thursday, September 14, 2017 — Poster Session III
- NG Lue
- AM Awe
- J Zhang
- M Pandey
- WF Simonds
The GNB5 gene encodes for the highly conserved fifth isoform of the ß subunit of the heterotrimeric Gproteins (Gß5). Unlike other isoforms, Gß5 does not bind to the alpha and gamma subunits associated with the G-protein coupled receptor (GPCR), and rather forms the Gß5/R7-RGS complex. This complex, anchored to the plasma membrane by the protein R7bp, regulates the GPCR signaling via GAP (GTPase Activating Protein) activity on the G a i/o subunit. Previous research on Gß5 in mice has shown that homozygous knockout of GNB5 results in marked developmental delays, motor activity deficits, and structural differences in the hippocampal dentate gyrus, which is critical for learning and special encoding. Motor, speech, and attention deficits have also been observed in humans with homozygous loss of GNB5. Although 2% of the population is estimated to harbor damaging mutations in the GNB5 gene, little is known about the GNB5 heterozygous phenotypes. Here we focus on differences in overall glia, microglia, and neuronal apoptosis in the hippocampal dentate gyrus of GNB5 +/- mice in comparison to wildtype mice. These results indicate that there are significant compositional abnormalities in the dentate gyrus, which may alter spatial navigation and behavior relating to learning and memory formation.