Ben Smith

Joined Program: 2004
Prior Training: B.S. Biology, University of Southern Maine
Braun Lab
llamero [ a t ] u.washington.edu

Research:
Androgen receptor is expressed in many cell types within the testis and is known to be necessary for spermatogenesis. The exact mechanism through which androgen receptor regulates spermatogenesis remains poorly understood, however recent insights from microarray data and subsequent follow-up experiments suggest a role for androgen receptor in regulating Sertoli cell tight junctions; one of the most impermeable barriers in mammals.

Hypothesis: Androgen receptor regulates the composition of the Sertoli tight junction.

Aim 1: Characterize the impact androgen receptor expression has on the composition of the Sertoli cell tight junction. Mice with a Sertoli cell specific knockout of the androgen receptor allele will be analyzed for shifts in the mRNA levels of known tight junction genes, changes in the localization of tight junction proteins within the Sertoli cell, and changes in the quantity of known Sertoli cell tight junction protein, as well as changes in their phosphorylation state.

Aim 2: Characterize the effect of ectopic expression of Claudin-3, a tight junction protein believed to be regulated by androgen receptor, in Sertoli cells. Claudin-3 will be ectopically expressed in mouse Sertoli cells via a Sertoli-specific inducible Claudin-3 allele. The mice will then be screened for such properties as testis histology, proper spermatogenesis, sperm count, serum sex hormone levels, and biotin tracer penetration past the Sertoli cell tight junction and into the lumen of the seminiferous tubules.