ORCID
https://orcid.org/0000-0002-0148-2211
Date of Award
2024
Document Type
Thesis
Degree Name
MS in Biology
Department
Biological Sciences
First Advisor
YONG YU
Second Advisor
YAN ZHU
Third Advisor
MATTEO RUGGIU
Abstract
Polycystin-2 (PC2) is an ion channel belonging to the polycystin subfamily of the transient receptor potential (TRP) cation channel superfamily. Mutations in PC2 are associated with autosomal dominant polycystic kidney disease (ADPKD), one of the most common genetic diseases in humans. Despite extensive studies over the past decades, the role of PC2 in normal and ADPKD kidneys remains largely unknown, and the activation and regulation of this ion channel are elusive. To gain a better understanding of the structure and function of the mouse PC2 channel, this study focused on generating five pore mutations in a gain-of-function (GOF) mutant of mouse PC2 (mPC2-AA) and assessing their functional effects. Results indicated that four of these mutations abolished mouse PC2 channel activity when expressed in Xenopus oocytes. Meanwhile, the N672C mutation not only preserved mouse PC2 channel function but also resulted in increased Ca2+ permeability. These novel mutations provide valuable insights for generating mouse models for ADPKD studies. In a parallel line of investigation, a proline mutagenesis screen was conducted on the fifth transmembrane segment (S5) to identify a more suitable GOF mutation of mouse PC2. Ten mutations were generated and tested for their effects on mouse PC2 channel function. Although none of the tested mutations exhibited the desired GOF effect, these findings contribute to a deeper understanding of the structure and function of the mPC2 channel.
Recommended Citation
Pillai, Akhilraj Rajan, "SEARCHING FOR NOVEL MUTATIONS THAT REGULATES THE MOUSE POLYCYSTIN-2 (TRPP2) ION CHANNEL" (2024). Theses and Dissertations. 751.
https://scholar.stjohns.edu/theses_dissertations/751