No obvious phenotypic abnormalities in mice lacking the Pate4 gene

TY - JOUR

T1 - No obvious phenotypic abnormalities in mice lacking the Pate4 gene

AU - Heckt, Timo

AU - Keller, Johannes

AU - Reusch, Roswitha

AU - Hartmann, Kristin

AU - Krasemann, Susanne

AU - Hermans-Borgmeyer, Irm

AU - Amling, Michael

AU - Schinke, Thorsten

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2016/1/22

Y1 - 2016/1/22

N2 - We have previously reported that the hormone calcitonin (CT) negatively regulates bone formation by inhibiting the release of sphingosine-1-phosphate from bone-resorbing osteoclasts. In the context of this study we additionally observed that CT repressed the expression of Pate4, encoding the secreted protein caltrin/Svs7, in osteoclasts from wildtype mice. To assess a possible function of Pate4 in bone remodeling, we utilized commercially available embryonic stem cells with a targeted Pate4 allele to generate Pate4-deficient mice. These were born at the expected Mendelian ratio and did not display obvious abnormalities until the age of 6 months. A bone-specific histomorphometric analysis further revealed that bone remodeling is unaffected in male and female Pate4-deficient mice. Since a subsequently performed multi-tissue expression analysis confirmed that Pate4 is primarily expressed in prostate and seminal vesicles, we additionally analyzed the respective tissues of Pate4-deficient mice, but failed to detect histological abnormalities. Most importantly, as assessed by mating with female wildtype mice, we did not observe reduced fertility associated with Pate4-deficiency. Taken together, our study was the first to generate and analyze a mouse model lacking Pate4, a gene with strong expression in prostate and seminal vesicles, yet without major function for fertility.

AB - We have previously reported that the hormone calcitonin (CT) negatively regulates bone formation by inhibiting the release of sphingosine-1-phosphate from bone-resorbing osteoclasts. In the context of this study we additionally observed that CT repressed the expression of Pate4, encoding the secreted protein caltrin/Svs7, in osteoclasts from wildtype mice. To assess a possible function of Pate4 in bone remodeling, we utilized commercially available embryonic stem cells with a targeted Pate4 allele to generate Pate4-deficient mice. These were born at the expected Mendelian ratio and did not display obvious abnormalities until the age of 6 months. A bone-specific histomorphometric analysis further revealed that bone remodeling is unaffected in male and female Pate4-deficient mice. Since a subsequently performed multi-tissue expression analysis confirmed that Pate4 is primarily expressed in prostate and seminal vesicles, we additionally analyzed the respective tissues of Pate4-deficient mice, but failed to detect histological abnormalities. Most importantly, as assessed by mating with female wildtype mice, we did not observe reduced fertility associated with Pate4-deficiency. Taken together, our study was the first to generate and analyze a mouse model lacking Pate4, a gene with strong expression in prostate and seminal vesicles, yet without major function for fertility.

U2 - 10.1016/j.bbrc.2015.12.104

DO - 10.1016/j.bbrc.2015.12.104

M3 - SCORING: Journal article

C2 - 26731031

VL - 469

SP - 1069

EP - 1074

JO - BIOCHEM BIOPH RES CO

JF - BIOCHEM BIOPH RES CO

SN - 0006-291X

IS - 4

ER -