Gene trap mutation of murine Outer dense fiber protein-2 gene can result in sperm tail abnormalities in mice with high percentage chimaerism

Abstract

BackgroundOuter dense fiber protein 2, Odf2, is a major component of the outer dense fibers, ODF, in the flagellum of spermatozoa. ODF are associated with microtubule doublets that form the axoneme. We recently demonstrated that tyrosine phosphorylation of Odf2 is important for sperm motility. In the course of a study of Odf2 using Odf2 mouse knockout lines we observed that males of a high percentage chimaerism, made using XL169 embryonic stem cells, were infertile, whereas mice of low-medium percentage chimaerism were fertile.ResultsXL169 ES cells have a β-geo gene trap cassette inserted in the Odf2 gene. To determine possible underlying mechanisms resulting in infertility we analyzed epididymal sperm and observed that >50% displayed bent tails. We next performed ultrastructural analyses on testis of high percentage XL169 chimaeric mice. This analysis showed that high percentage XL169 chimaeric mice produce elongating spermatids that miss one or more entire outer dense fibers in their midpiece and principal piece. In addition, we observed elongating spermatids that show thinning of outer dense fibers. No other obvious abnormalities or defects are present in elongating spermatids. Spermatozoa from the caput and cauda epididymis of XL169 mice of high percentage chimaerism show additional tail defects, including absence of one or more axonemal microtubule doublets and bent tails. Sperm with bent tails display abnormal motility.ConclusionsOur results document the possible impact of loss of one Odf2 allele on sperm tail structure and function, resulting in a novel sperm tail phenotype.

The role of chromatoid bodies and cytoskeleton in differentiation of rat spermatozoids

“…Therefore, we suggested that GA may be a source of components required for the regulation of differentiation process. The proposal is supported by data in the literature (Anton, 1983;Thorne Tjomsland et al, 1988). The authors reported that vesicles that were CB components exhibited acid phosphatase activity and NADPase and/or CMPase properties common for GA compartments.…”

“…ODF con sists of seven major proteins and a number of partially characterized less abundant proteins (Shao et al, 1997(Shao et al, , 1999Kim et al, 1999;Petersen et al, 1999;Ricci and Breed, 2001;Tarnasky et al, 2010). It appeared that the ODF2 protein required for the sper matozoid normal mobility is of centrosome origin (Nakagawa et al, 2001;Tarnasky et al, 2010).…”

The Australian saltwater crocodile (Crocodylus porosus) provides evidence that the capacitation of spermatozoa may extend beyond the mammalian lineage

“…Similarly, outer dense fibre of sperm tails 2 (ODF2) also serves as an important element of the cytoskeletal structures that surround the axoneme within the mid-and principal piece of the sperm tail [54]. This protein is instrumental in regulating the elasticity and recoil of the sperm tail, with defects leading to abnormal sperm morphology and compromised fertility [55]. As an important proof-of-concept, ODF2 is also recognized as an important target for cAMPdriven phosphorylation [56].…”

Functional aspects of seminal plasma and sperm proteins and their potential as molecularmarkers of fertility

“…Sperm proteins play important roles in sperm integrity, morphology and functions, including motility, capacitation, fertilization, egg activation and embryo development (Parisi et al, 2014). For example, Outer dense fiber protein 2 (ODF2) is a component of sperm tail structure and is involved in regulation of motility in mouse (Tarnasky et al, 2010). In addition, tubulins, such as tubulin beta-2C chain located in sperm tail, are down regulated in asthenozoospermia (Siva et al, 2010).…”