TALEN-mediated editing of the mouse Y chromosome

The functional study of Y chromosome genes has been hindered by a lack of mouse models with specific Y chromosome mutations. We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes – Sry and Uty. TALEN-mediated gene editing is a useful tool for dissecting the biology of the Y chromosome. The Y chromosome has unique structure and gene content and has evolved into a chromosome that is highly specialized for male sex differentiation and fertility1, 2. A comprehensive approach to study the function of Y-linked genes in mice is needed to unravel the biology of the Y chromosome. Perhaps due to the unique structural features of the Y chromosome, conventional gene targeting strategies in mESCs to generate mutations in Y-linked genes have been unsuccessful. Therefore, our understanding of the functions of murine Y-linked genes is limited to insights gained from studies of mice that carry spontaneous deletions, random gene trap insertions or autosomal transgenes3-5. Although two Y-linked knockout mESC clones and one transgenic mouse line have been generate