Male Mice Lacking the Theg (Testicular Haploid Expressed Gene) Protein Undergo Normal Spermatogenesis and Are Fertile1

Abstract

The testicular haploid expressed gene (Theg) encodes for a novel approximately 42.0-kDa nuclear protein, which is specifically expressed in spermatid cells. Its expression is upregulated by some unknown factor(s) from Sertoli cells. To elucidate the function of Theg protein and its role in spermatogenesis, we disrupted the Theg locus in mouse by homologous recombination. For functional dissection of the domain structure of the Theg protein, two different knockout approaches were undertaken. In the first knockout mouse (Th14), the C-terminal region of the Theg protein (amino acids 137-376) was deleted. Both Th14+/- and Th14-/- mice from genetic backgrounds of C57BL/6J x 129X1/SvJ hybrid and 129X1/SvJ inbred exhibited a normal phenotype and were fertile. The testes of Th14-/- mice were smaller than those of Th14+/- and Th14+/+ mice; however, the testicular morphology and the properties of sperm, including morphology and motility, from Th14-/- mice were similar to those of Th14+/- and Th14+/+ mice. These results demonstrate that the C-terminal region of Theg (amino acids 137-376) does not play an important role in progression of spermatogenesis. In the second knockout mouse (Th15), we deleted the N-terminal domain of the Theg protein, which resulted in complete loss of Theg transcripts. Both Th15+/- and Th15-/- mice from genetic backgrounds C57BL/6J x 129X1/SvJ hybrid, C3H/J congenic, and 129X1/SvJ inbred appeared normal and were fertile, with no gross abnormalities detected in testicular morphology or sperm properties. Our results from both knockout mouse model systems clearly illustrate that Theg is not essential for spermatogenesis in the mouse.

Increased expression of cellular retinol-binding protein 1 in laryngeal squamous cell carcinoma

“…In the case of the benign lesions, both samples exhibited small number of molecular alterations mainly DNA gains but none of those alterations were shared between all samples. Only a loss in the testicular haploid expressed gene in subtelomeric region of the long arm of chromosome 19 (Mannan et al 2003) was shared between these two samples. For larynx tumours, the most common DNA gain (10/19 samples, 52.6%) was found in the spot corresponding to CRBP-1 gene followed by EGFR gene (9/19 samples, 47.3%).…”

A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets

“…These results, coupled with a search of the literature for other genes in the five clusters, show that 17 of 19 germ cell-specific genes eliminated by homologous recombination are essential for normal male fertility (Table 6, which is published as supporting information on the PNAS web site). The genes include proteases or proteins that interact with proteases (14-17), protein kinases, or proteins that interact with protein kinases (18), transcription factors (19), proteins associated with chromatin (20)(21)(22), channels or transporters (1, 23), mitochondrial-associated proteins (24,25), adhesion proteins (26), RNA polymerases (27), and genes involved in the interaction between spermatids and Sertoli cells (28). More than 50% of these genes result in a complete loss of fertility when disrupted.…”

Prm3, the Fourth Gene in the Mouse Protamine Gene Cluster, Encodes a Conserved Acidic Protein That Affects Sperm Motility1

“…Prm3 resembles a variety of male germ cell-specific genes that exhibit little or no effect on male fertility in gene knockouts, including Theg, Hist1h1t, proacrosin, calgizarrin calspermin, Smcp, Creb3l4, and testatin [39,[44][45][46][47][48][49][50][51][52][53][54]. The observation that targeted deletion of conserved genes that are expressed in spermatogenic cells often has modest effects on male fertility has multiple explanations.…”