Cloning and Expression Analysis of Testis-Specific Cyclic 3′,5′-Adenosine Monophosphate-Responsive Element Modulator Activators in the Nonhuman Primate (Macaca fascicularis): Comparison with Other Primate and Rodent Species1

The cAMP-responsive element modulator (CREM) gene encodes a transcription factor that is essential for spermatogenesis. In mouse testis, several CREM repressors and activators have been identified. In contrast to the situation for the mouse, however, little is known about CREM isoforms in the primate testis. We analyzed CREM isoforms and mRNA expression in a clinically relevant primate model, the cynomolgus monkey (Macaca fascicularis). A cDNA library was generated from monkey testis; and two activator isoforms (tau2 with and without exon gamma) were identified, which displayed high sequence identity to mouse and human isoforms. The insertion of exon gamma was observed for the first time in the primate testis. CREM activator expression was confined to the testis, where it was seen in late pachytene spermatocytes and round spermatids in specific spermatogenic stages, as revealed by in situ hybridization. Comparison of the mRNA and the recently described protein expression indicated a lack of translational delay of CREM expression. Comparative analysis of testicular CREM expression by reverse transcription-polymerase chain reaction yielded several transcripts in the rat, mouse, hamster, and marmoset; two transcripts in cynomolgus and rhesus monkeys; and one transcript in men. These findings suggest an evolutionary trend from multiple activator isoforms to a single activator transcript in men.