V225G Mutation Increases Stability of KPNA3 Thereby Contributing to an Age-Dependent Hyperactive Phenotype in C57BL/6J Mice
In: Student Reports, Summer 2021, The Jackson Laboratory
Yehya Barakat Predoctoral Associate, and Vivek Kumar, Ph.D.
The mechanisms through which genetic variation regulates complex behavioral phenotypes is of considerable interest for health and disease. Certain alleles predispose individuals to disease while others are protective. Identification of such variants and their mechanistic roles in essential cellular processes such as synaptic regulation or nuclear localization is important for therapeutic interventions. In a forward genetic screen, the Kumar Lab identified a mutation in karyopherin α-3 (KPNA3) identified that potentially leads to age dependent hyperactivity in the open field assay. KPNA3 is a nuclear importin protein that bind to substrates utilizing various nuclear export signals (NES) and nuclear localization signals (NLS), translocate the substrate across the nuclear pore complex, and release it on the opposite side of the nuclear membrane. Here I investigated whether and how the candidate mutation of valine to glycine (V225G) in KPNA3 affects its stability. I found that the KPNA3 V225G mutation increases its stability suggesting that prolonged or increased presence of KPNA3 in the cell may be key to the development of a hyperactive phenotype in C57BL/6J mice.
Guardado, Ryan, "V225G Mutation Increases Stability of KPNA3 Thereby Contributing to
an Age-Dependent Hyperactive Phenotype in C57BL/6J Mice" (2021). Summer and Academic Year Student Reports. 2664.