Generation of transgenic mice: Replacement of vasectomized males by genetically sterile males

Vasectomy is a surgical procedure (severity level of 2) which until now is indispensable for the preparation of males which are subsequently used to induce pseudopregnancy in foster females. Such females are required for strain rederivation by embryo transfer (ET) as well as other techniques that involve ET such as the production of transgenic and “knock‐ out” mice. We have recently refined all ET‐dependant methods by generating a transgenic mouse strain carrying a dominant male‐specific sterility trait. Males from such a strain could be used directly to induce pseudopregnancy in females thus making the vasectomy procedure redundant. We generated several transgenic mouse lines expressing a Protamine‐1 (Prm1) EGFP fusion protein under the transcriptional and translational regulatory control of Prm1. Male mice from lines showing strong overexpression of the Prm1‐EGFP fusion protein resulted in com‐ plete and dominant male sterility without affecting the ability to mate and to produce copulatory plugs. Sterility was due to impaired spermatid maturation affecting sperm viability and motility. The “genetic vasectomy system” was further improved by genetically linking the dominant male sterility to ubiquitous EGFP expression in the soma as an easy phenotypic marker enabling rapid genotyping of trans‐ genic males and females. This double transgenic approach represents a reliable and cost‐ effective “genetic vasectomy” procedure mak‐ ing the conventional surgical vasectomy obsolete

Reference: Haueter S., Kawasumi M., Asner I., Brykczynska U., Cinelli P., Moisyad S., Bürki K., Peters A.H. and Pelczar P. (2010): Genetic vasectomy – overexpression of Prm1‐EGFP fusion protein in elongating spermatids causes dominant male sterility in mice. Genesis 48, 151‐160. Download original publication (PDF)