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Genetic vasectomy-overexpression of Prm1-EGFP fusion protein in elongating spermatids causes dominant male sterility in mice


Haueter, S; Kawasumi, M; Asner, I; Brykczynska, U; Cinelli, P; Moisyadi, S; Bürki, K; Peters, A H F M; Pelczar, P (2010). Genetic vasectomy-overexpression of Prm1-EGFP fusion protein in elongating spermatids causes dominant male sterility in mice. Genesis: The Journal of Genetics and Development, 48(3):151-160.

Abstract

Transgenic mice are vital tools in both basic and applied research. Unfortunately, the transgenesis process as well as many other assisted reproductive techniques involving embryo transfer rely on vasectomized males to induce pseudopregnancy in surrogate mothers. Vasectomy is a surgical procedure associated with moderate pain and must be carried out under full anaesthesia by qualified personnel. Eliminating the need for vasectomy would be beneficial from the economic and animal welfare point of view. Our aim was to develop a transgene-based alternative to the surgical vasectomy procedure. 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 moderate transgene expression were fully fertile whereas strong overexpression of the Prm1-EGFP fusion protein resulted in complete 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. Furthermore, sperm having high Prm1-EGFP levels failed to support preimplantation embryonic development following Intracytoplasmic Sperm Injection (ICSI). 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 transgenic males and females. This double transgenic approach represents a reliable and cost-effective "genetic vasectomy" procedure making the conventional surgical vasectomy methodology obsolete. genesis 00:1-10, 2010. (c) 2010 Wiley-Liss, Inc.

Abstract

Transgenic mice are vital tools in both basic and applied research. Unfortunately, the transgenesis process as well as many other assisted reproductive techniques involving embryo transfer rely on vasectomized males to induce pseudopregnancy in surrogate mothers. Vasectomy is a surgical procedure associated with moderate pain and must be carried out under full anaesthesia by qualified personnel. Eliminating the need for vasectomy would be beneficial from the economic and animal welfare point of view. Our aim was to develop a transgene-based alternative to the surgical vasectomy procedure. 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 moderate transgene expression were fully fertile whereas strong overexpression of the Prm1-EGFP fusion protein resulted in complete 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. Furthermore, sperm having high Prm1-EGFP levels failed to support preimplantation embryonic development following Intracytoplasmic Sperm Injection (ICSI). 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 transgenic males and females. This double transgenic approach represents a reliable and cost-effective "genetic vasectomy" procedure making the conventional surgical vasectomy methodology obsolete. genesis 00:1-10, 2010. (c) 2010 Wiley-Liss, Inc.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Laboratory Animal Science
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:03 Mar 2010 13:54
Last Modified:20 Sep 2016 06:15
Publisher:Wiley-Blackwell
ISSN:1526-954X
Publisher DOI:https://doi.org/10.1002/dvg.20598
PubMed ID:20095053

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