Sodium/hydrogen exchangers (NHEs) are a family of vital transmembrane proteins responsible for facilitating ion transport and thus regulating intracellular pH as well as cell volume. Certain NHEs have been shown to be necessary for sperm motility and thus fertility, and there are many different isoforms expressed in sperm cells. However, the specific physiological role of all NHE isoforms in sperm cells and therefore male fertility is not yet fully understood. NHE1 is one of such isoforms expressed in the midpiece of sperm flagella. This study seeks to decipher the role of NHE1 in sperm motility and male fertility. To achieve this, male Mus musculus mice will be used to create a NHE1 gene knockout (KO) mice model with perturbed NHE1 expression in the testes and sperm but expression of NHE1 in the brain (as NHE1 is the major and NHE in the brain). Without NHE1 expression in the brain, mice exhibit a recurring brain seizure phenotype and would not live to sexual maturity, so we could not observe the resulting sperm functionality. To produce NHE1 KO sperm cells, I will generate a transgenic mouse line that expresses NHE1 under the control of the brain specific promoter Thy1, which will then be crossed into the NHE1 knockout line so that mice can express NHE1 in the brain from the transgene, but lack NHE1 expression in all other tissues. Observations can then be made of phenotypic changes in isolated sperm cells and the reproduction of NHE1 KO mice. Results will be compared to the wild type mice phenotype with unperturbed expression of NHE1. This targeted KO strategy will uncover the role of NHE1 protein in sperm motility, fertility, and ultimately reproduction.
Author: Sydney Anas
Faculty Advisor: Paul James, Biology
Graduate Student Advisor: Odunayo Ayodele, Biology
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