A novel PSMA/GCPII-deficient mouse model shows enlarged seminal vesicles upon aging

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10386514" target="_blank" >RIV/00064203:_____/19:10386514 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68378050:_____/19:00501452 RIV/61388963:_____/19:00501452 RIV/00216208:11110/19:10386514 RIV/00216208:11130/19:10386514 a 2 dalších

Výsledek na webu

<a href="https://doi.org/10.1002/pros.23717" target="_blank" >https://doi.org/10.1002/pros.23717</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/pros.23717" target="_blank" >10.1002/pros.23717</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A novel PSMA/GCPII-deficient mouse model shows enlarged seminal vesicles upon aging

Popis výsledku v původním jazyce

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 &lt; 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.

Název v anglickém jazyce

A novel PSMA/GCPII-deficient mouse model shows enlarged seminal vesicles upon aging

Popis výsledku anglicky

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 &lt; 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Prostate

ISSN

0270-4137

e-ISSN

—

Svazek periodika

79

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

126-139

Kód UT WoS článku

000453562300002

EID výsledku v databázi Scopus

2-s2.0-85052954730