Abstract
The inhibitory G protein Gαo is the most abundant G protein in the brain, yet its signaling mechanism is incompletely understood. To better understand the mechanism and physiological role of Gαo signaling, we generated a knock–in mouse with a mutation (G184S) that enhances Gαo‐mediated signaling. Homozygous GαoG184S/G184S mice die shortly after birth. Born at Mendelian ratios, none survive 24 hours. The heterozygous GαoG184S/+ mice are viable and appear normal up to ~12 weeks of age. After this time, they show a strain‐dependent lethality ‐ mice on a 129/SvJ background live more than a year but after back‐crossing onto a C57BL/6J background about half die between 12 and 30 weeks of age. Weight, grooming, and behavior appear normal up to 24 hours prior to death. To identify novel genes that may modify Gαo signaling or physiological functions involved in sudden death, we undertook a genome‐wide SNP analysis. Potential modifiers of this phenotype were identified on Chromosome 17. Future studies will use this model to attempt to understand both Gαo‐mediated signaling and the potential causes and significance of this novel sudden model. Supported by RO1‐GM39561 (RRN) and 5T32GM008322 (JMK).
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
