| First Author | Vorlová B | Year | 2019 |
| Journal | Prostate | Volume | 79 |
| Issue | 2 | Pages | 126-139 |
| PubMed ID | 30256431 | Mgi Jnum | J:283327 |
| Mgi Id | MGI:6386106 | Doi | 10.1002/pros.23717 |
| Citation | Vorlova B, et al. (2019) A novel PSMA/GCPII-deficient mouse model shows enlarged seminal vesicles upon aging. Prostate 79(2):126-139 |
| abstractText | 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. |
