Abstract
Subunit Kir6.1 and SUR2B form a subtype of ATP sensitive potassium channel (KATP) which is mainly expressed in vascular, gastrointestinal and lymphatic smooth muscles controlling the muscle contractility tones. Gain-of-function mutations of this channel lead to Cantu Syndrome, featured with hypertrichosis, coarse facial expression, cardiac hypertrophy and sometimes lymphedema. Conventional patch-clamp assays are available for studying the consequences of Cantu Syndrome, however, the throughput is low. In this thesis, two higher throughput fluorescence -based assays, thallium flux assay and DiBAC4(3) assay with unique capabilities of large and small current detections respectively were developed for more comprehensive mutation characterizations together with patch-clamp. Multiple previously studied and new clinically discovered Cantu Syndrome mutations were assessed, revealing novel molecular mechanisms of channel gain of function and revealing mutational consequences for drug sensitivity, and providing insights both for clinical diagnosis and potential therapies for Cantu Syndrome.
Committee Chair
Colin Nichols
Committee Members
Dorothy Katherine Grange; Jerod Denton; Jianmin Cui; Jonathan Silva
Degree
Doctor of Philosophy (PhD)
Author's Department
Biomedical Engineering
Document Type
Dissertation
Date of Award
11-21-2024
Language
English (en)
DOI
https://doi.org/10.7936/pyyq-az23
Recommended Citation
Gao, Jian, "Molecular Diagnosis of Cantu Syndrome: Implications for KATP Channel Function and Drug Therapy" (2024). McKelvey School of Engineering Theses & Dissertations. 1129.
The definitive version is available at https://doi.org/10.7936/pyyq-az23