Understanding testis development in mouse models of ATR-X syndrome

Abstract

ATR-X syndrome is a Disorder of Sex Development (aka ‘intersex’) that affects males and is characterized by alpha thalassemia, intellectual disability, and genital anomalies (80%) including small testes. We developed mouse models to study the testis defects in ATR-X syndrome. We found that the testes begin to degenerate from mid-gestation because the Y chromosome is damaged when the ATRX protein is missing – this led us to identify an unusual novel structure we call a giant GATA4-PML NB in the nucleus of dying testicular Sertoli cells. In summary, ATRX is needed to compact the Y chromosome during testis growth.