Testicular degeneration in a rat model expressing p.R106C TFG

Abstract

Despite a majority of proteins depending on the early secretory pathway for export, the precise role of this machinery in development and maintenance of tissue architecture is largely unknown. The p.R106C mutation in Trk-fused Gene (TFG), a highly conserved component of the early secretory pathway underlies a recessive form of hereditary spastic paraplegia (HSP). Using a rodent model carrying the disease-associated mutation, we observed that R106C homozygous males exhibit infertility and a striking disorganization of testicular morphology by 8 weeks of age. In this thesis, we examine testes pathomorphology to show that the observed phenotype is best described by degeneration following a period of typical development. Qualitative analysis of histology suggests that disrupted junctions between seminiferous tubules may be to blame for this observation. This work lays a groundwork to explore which cargoes’ transport is disrupted by the p.R106C mutation, and how different cell types of the testes are affected.