A gene trap knockout of the abundant sperm tail protein, outer dense fiber 2, results in preimplantation lethality

Abstract

SummaryOuter dense fiber 2 (Odf2) is highly expressed in the testis where it encodes a major component of the outer dense fibers of the sperm flagellum. Furthermore, ODF2 protein has recently been identified as a wide-spread centrosomal protein. While the expression of Odf2 highlighted a potential role for this gene in male germ cell development and centrosome function, the in vivo function of Odf2 was not known. We have generated Odf2 knockout mice using an Odf2 gene trapped embryonic stem cell (ESC) line. Insertion of a gene trap vector into exon 9 resulted in a gene that encodes a severely truncated protein lacking a large portion of its predicted coil forming domains as well as both leucine zipper motifs that are required for protein-protein interactions with ODF1, another major component of the outer dense fibers. Although wild-type and heterozygous mice were recovered, no mice homozygous for the Odf2 gene trap insertion were recovered in an extended breeding program. Furthermore, no homozygous embryos were found at the blastocyst stage of embryonic development, implying a critical pre-implantation role for Odf2. We show that Odf2 is expressed widely in adults and is also expressed in the blastocyst stage of preimplantation development. These findings are in contrast with early studies reporting Odf2 expression as testis specific and suggest that embryonic Odf2 expression plays a critical role during preimplantation development in mice.

Sperm dysfunction and ciliopathy

“…One of the basal foot proteins, ODF2, is necessary for both basal foot formation and orientation of the ciliary beat [117]. ODF2-knockout mice show embryonic lethality [118], in agreement with the observation that ODF2 is a basic component of the mother centriole. ODF2 was originally found as a component of ODF of sperm tail [119].…”

HRP2 determines the efficiency and specificity of HIV-1 integration in LEDGF/p75 knockout cells but does not contribute to the antiviral activity of a potent LEDGF/p75-binding site integrase inhibitor

“…Thus, the impact of the KO relies on the efficiency of the trap (40,41). MEF cells isolated from 13.5-day post-cotium embryos were adapted for long-term culture by transformation with SV40 large T antigen as described (31).…”

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 3: Developmental changes in spermatid flagellum and cytoplasmic droplet and interaction of sperm with the zona pellucida and egg plasma membrane

“…While ODF2 is predominant in the testis, it is ubiquitously expressed (Huber and Hoyer-Fender, 2007). Transgenic mice expressing a truncated form of ODF2 show preimplantation lethality (Salmon et al, 2006). A sperm cytoskeletal protein TSA70 is expressed postmeiotically in a stage-specific manner, where it localizes to the tail of spermatozoa.…”