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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2010

Open Access 01-12-2010 | Research

Genetic evidence that SMAD2 is not required for gonadal tumor development in inhibin-deficient mice

Authors: Saneal Rajanahally, Julio E Agno, Roopa L Nalam, Michael B Weinstein, Kate L Loveland, Martin M Matzuk, Qinglei Li

Published in: Reproductive Biology and Endocrinology | Issue 1/2010

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Abstract

Background

Inhibin is a tumor-suppressor and activin antagonist. Inhibin-deficient mice develop gonadal tumors and a cachexia wasting syndrome due to enhanced activin signaling. Because activins signal through SMAD2 and SMAD3 in vitro and loss of SMAD3 attenuates ovarian tumor development in inhibin-deficient females, we sought to determine the role of SMAD2 in the development of ovarian tumors originating from the granulosa cell lineage.

Methods

Using an inhibin α null mouse model and a conditional knockout strategy, double conditional knockout mice of Smad2 and inhibin alpha were generated in the current study. The survival rate and development of gonadal tumors and the accompanying cachexia wasting syndrome were monitored.

Results

Nearly identical to the controls, the Smad2 and inhibin alpha double knockout mice succumbed to weight loss, aggressive tumor progression, and death. Furthermore, elevated activin levels and activin-induced pathologies in the liver and stomach characteristic of inhibin deficiency were also observed in these mice. Our results indicate that SMAD2 ablation does not protect inhibin-deficient females from the development of ovarian tumors or the cachexia wasting syndrome.

Conclusions

SMAD2 is not required for mediating tumorigenic signals of activin in ovarian tumor development caused by loss of inhibin.
Appendix
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Metadata
Title
Genetic evidence that SMAD2 is not required for gonadal tumor development in inhibin-deficient mice
Authors
Saneal Rajanahally
Julio E Agno
Roopa L Nalam
Michael B Weinstein
Kate L Loveland
Martin M Matzuk
Qinglei Li
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2010
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-8-69

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