A novel PSMA/GCPII‐deficient mouse model shows enlarged seminal vesicles upon aging. Issue 2 (5th September 2018)

• Record Type: Journal Article
• Authors: Vorlová, Barbora; Sedlák, František; Kašpárek, Petr; Šrámková, Karolína; Malý, Marek; Zámečník, Josef; Šácha, Pavel; Konvalinka, Jan
• Is Part Of: Prostate. Volume 79:Issue 2(2019)
• Page Start: 126
• Page End: 139
• Publication Date: 2018-09-05
• Subjects: dilated seminal vesicles -- Folh1 -- glutamate carboxypeptidase II -- knockout mice -- prostate‐specific membrane antigen; Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.23717
• Languages: English
• ISSNs: 0270-4137

Abstract

Abstract : 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.