The Use of Transgenic Mouse Models in the Study of Male Infertility

Abstract

Over the past few decades with the rapid advances in embryo and embryonic stem cell manipulation techniques, transgenic mouse models have emerged as a powerful tool for the study of gene function and complex diseases including male infertility. In this review we give a brief history of the development of tools for the production of transgenic mouse models. This spans the advances from early pronuclear injection to the use of targeted embryonic stem cells to produce gene targeted, conditional, and inducible knockout mouse models. Lastly we provide a few examples to illustrate the utility of mouse models in the study of male infertility.

Truncating mutations inTAF4BandZMYND15causing recessive azoospermia

“…The best-known genetic cause of isolated spermatogenetic failure is Yq11 microdeletions, and heterozygous mutations or polymorphisms in a few other genes have been described. Considering that more than 2300 genes are estimated to play a role in human spermatogenesis27 and that knockout mouse models indicate that close to 400 genes are involved in spermatogenesis,28 the number of known genes with roles in monogenic inheritance for spermatogenic failure in men is very small. Perhaps because most research has been conducted on mainly outbred populations, no recessive genes for idiopathic azoospermia had been identified up to now.…”

Pesticide Exposures Induce Male-Mediated Reproductive Toxicity: A Review

“…Increasing the sperm cell abnormalities specifically DNA damage were reported in several cases either human exposed to Polychlorinated biphenyls (Rignell-Hydbom et al, 2005) also in animal studies exposed to Methamidophos Methyl-Parathion (Piña-Guzmán et al, 2006), Imidacloprid (Bal et al, 2012) and Fenitrothion (Taib et al, 2014). Spermatogenesis is essential for the production of offspring whereby it is regulated by an estimation of more than 2300 genes (Tamowski et al, 2010). An irrevocable partial or complete spermatogenic arrest can occur as a result of genetic aberrations (Shamsi et al, 2011).…”

Genome Editing in Mice Using CRISPR/Cas

“…This includes that CRISPR/ Cas9, in its basic form generates mice with ubiquitous genetic manipulations, and at the time of writing its use to generate conditional knockouts/knockins is not widespread. Traditional methods of genetic manipulation allow for conditional knockouts through use of the Cre/LoxP or Flp/Frt systems (Menke 2013 ;Tamowski et al 2010 ). This is highly useful for analysing gene functions in certain tissues or at certain stages of the life cycle (Dymecki 1996 ;Feil et al 1996 ;Gossen and Bujard 1992 ;Sauer et al 1987 ;Tamowski et al 2010 ).…”

“…Traditional methods of genetic manipulation allow for conditional knockouts through use of the Cre/LoxP or Flp/Frt systems (Menke 2013 ;Tamowski et al 2010 ). This is highly useful for analysing gene functions in certain tissues or at certain stages of the life cycle (Dymecki 1996 ;Feil et al 1996 ;Gossen and Bujard 1992 ;Sauer et al 1987 ;Tamowski et al 2010 ). The diffi culty in adapting CRISPR for this purpose lay in the need for two LoxP sites to be integrated in the same allele in the correct orientation, creating a fl oxed gene.…”