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A novel PSMA/GCPII‐deficient mouse model shows enlarged seminal vesicles upon aging
Author(s) -
Vorlová Barbora,
Sedlák František,
Kašpárek Petr,
Šrámková Karolína,
Malý Marek,
Zámečník Josef,
Šácha Pavel,
Konvalinka Jan
Publication year - 2019
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23717
Subject(s) - glutamate carboxypeptidase ii , phenotype , epididymis , immunohistochemistry , western blot , biology , dipeptidase , prostate , microbiology and biotechnology , medicine , immunology , enzyme , biochemistry , sperm , gene , cancer , botany
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.