BACKGROUND: Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is an important diagnostic and therapeutic target in prostate cancer. PSMA/GCPII is also expressed in many healthy tissues, but its function has only been established in the brain and small intestine. Several research groups have attempted to produce PSMA/GCPII-deficient mice to study the physiological role of PSMA/GCPII in detail. The outcomes of these studies differ dramatically, ranging from embryonic lethality to production of viable PSMA/GCPII-deficient mice without any obvious phenotype. METHODS: We produced PSMA/GCPII-deficient mice (hereafter also referred as Folh1-/- mice) by TALEN-mediated mutagenesis on a C57BL/6NCrl background. Using Western blot and an enzyme activity assay, we confirmed the absence of PSMA/GCPII in our Folh1-/- mice. We performed anatomical and histopathological examination of selected tissues with a focus on urogenital system. We also examined the PSMA/GCPII expression profile within the mouse urogenital system using an enzyme activity assay and confirmed the presence of PSMA/GCPII in selected tissues by immunohistochemistry. RESULTS: Our Folh1-/- mice are viable, breed normally, and do not show any obvious phenotype. Nevertheless, aged Folh1-/- mice of 69-72 weeks exhibit seminal vesicle dilation, which is caused by accumulation of luminal fluid. This phenotype was also observed in Folh1+/- mice; the overall difference between our three cohorts (Folh1-/- , Folh1+/- , and Folh1+/+ ) was highly significant (P < 0.002). Of all studied tissues of the mouse urogenital system, only the epididymis appeared to have a physiologically relevant level of PSMA/GCPII expression. Additional experiments demonstrated that PSMA/GCPII is also present in the human epididymis. CONCLUSIONS: In this study, we provide the first evidence characterizing the reproductive tissue phenotype of PSMA/GCPII-deficient mice. These findings will help lay the groundwork for future studies to reveal PSMA/GCPII function in human reproduction.
- MeSH
- antigeny povrchové genetika metabolismus MeSH
- glutamátkarboxypeptidasa II nedostatek genetika metabolismus MeSH
- imunohistochemie MeSH
- lidé MeSH
- membránové glykoproteiny nedostatek genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- semenné váčky enzymologie patologie MeSH
- stárnutí metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Cyclooxygenase is the enzyme responsible for the production of prostaglandins (PGs). This cyclooxygenase exists in two isoforms: cyclooxygenase-1 (COX-1) and cyclooxygense-2 (COX-2). In humans and primates high levels of COX-2 are detected in the seminal vesicle. Further, the main source of PGs in the semen of these species is from the seminal vesicle. In rodents, the source of PGs in semen is from the vas deferens and abundant levels of COX-2 are detected. A direct relation is thought to exist between COX-2 levels and the source of PGs in semen. Moreover, the role of COX-1 and COX-2 in the seminal vesicle of rodents is obscure. The present study aims at localizing COX-1 and COX-2 in the seminal vesicle of mice. Immunohistochemical staining and COX activity assay revealed COX-1 as a dominant isoform in the mouse seminal vesicle. On treatment with nimesulide – a preferential COX-2 inhibitor - no change in staining intensity and COX activity was observed. The total PG levels also appeared to be unaltered following nimesulide treatment. This confirms that nimesulide had no effect on COX-1. The results presented here suggest COX-1 is the dominant isoform in the mouse seminal vesicle and is responsible for PG synthesis.
- MeSH
- cyklooxygenasa 1 biosyntéza chemie metabolismus MeSH
- cyklooxygenasa 2 biosyntéza chemie metabolismus MeSH
- interpretace statistických dat MeSH
- mastné kyseliny chemie MeSH
- metabolismus lipidů účinky léků MeSH
- myši MeSH
- prostaglandiny biosyntéza chemie metabolismus MeSH
- semenné váčky enzymologie metabolismus účinky léků MeSH
- sulfonamidy chemie metabolismus MeSH
- Check Tag
- myši MeSH
