Human CREB3L4 blocking peptide

Creb3l4 belongs to the CREB/ATF family of transcription factors that are involved in mediating transcription in response to intracellular signaling. This study shows that Creb3l4 is expressed at low levels in all organs and in different stages of embryogenesis but is present at very high levels in the testis, particularly in postmeiotic male germ cells. In contrast to CREB3L4 in the human prostate, of which specific expression was detected, Creb3l4 transcripts in the mouse prostate could be detected only by RT-PCR. To identify the physiological function of Creb3l4, the murine gene was inactivated by replacement with the gene encoding green fluorescent protein. Surprisingly, Creb3l4-deficient mice were born at expected ratios, were healthy, and displayed normal long-term survival rates. Despite a significant reduction in the number of spermatozoa in the epididymis of Creb3l4(-/-) mice, the breeding of mutant males with wild-type females was productive and the average litter size was not significantly altered in comparison to wild-type littermates. Further analyses revealed that the seminiferous tubules of Creb3l4(-/-) mice contained all of the developmental stages, though there was evidence for increased apoptosis of meiotic/postmeiotic germ cells. These results suggest that Creb3l4 plays a role in male germ cell development, but its loss is insufficient to completely compromise the production of spermatozoa.

BACKGROUND/OBJECTIVES: Increased adipose tissue mass closely associates with the development of insulin resistance and type 2 diabetes mellitus. Previously, we reported that CREB3L4 expressed in adipose tissue negatively regulates adipogenesis, and Creb3l4 knockout mice fed a high-fat diet for 16 weeks showed fat cell hyperplasia, with improved glucose tolerance and insulin sensitivity. These mice did not show significant weight gain and fat mass. Because fat diet or aging is known to be associated with the development of obesity, we examined the effects of Creb3l4 gene subjected to low-fat diet (LFD) or aging process on body composition and obesity risk. SUBJECTS/METHODS: We fed Creb3l4 knockout mice a low-fat diet for 16 weeks (LFD group) or chow diet for over 1 year (aged group) and observed various metabolic parameters in the LFD-fed and aged Creb3l4 knockout mice. RESULTS: LFD-fed and aged Creb3l4 knockout mice showed significant weight gain and adiposity, impaired glucose tolerance and decreased insulin sensitivity, compared with wild-type mice. CONCLUSIONS: Creb3l4 has a critical role in metabolic phenotypes and a better understanding of its function may provide improved insight into the etiology of diabetes and other metabolic disorders.