A novel PSMA/GCPII-deficient mouse model shows enlarged seminal vesicles upon aging
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
30256431
DOI
10.1002/pros.23717
Knihovny.cz E-zdroje
- Klíčová slova
- Folh1, dilated seminal vesicles, glutamate carboxypeptidase II, knockout mice, prostate-specific membrane antigen,
- 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
- Názvy látek
- antigeny povrchové MeSH
- FOLH1 protein, human MeSH Prohlížeč
- glutamátkarboxypeptidasa II MeSH
- membránové glykoproteiny MeSH
- PSMA protein, mouse MeSH Prohlížeč
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.
1st Faculty of Medicine Charles University Prague 2 Czech Republic
Department of Biochemistry Faculty of Science Charles University Prague 2 Czech Republic
National Institute of Public Health Prague 10 Czech Republic
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