RGD Reference Report - Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. - Rat Genome Database

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Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice.

Authors: Pangas, SA  Li, X  Umans, L  Zwijsen, A  Huylebroeck, D  Gutierrez, C  Wang, D  Martin, JF  Jamin, SP  Behringer, RR  Robertson, EJ  Matzuk, MM 
Citation: Pangas SA, etal., Mol Cell Biol. 2008 Jan;28(1):248-57. Epub 2007 Oct 29.
RGD ID: 2299978
Pubmed: PMID:17967875   (View Abstract at PubMed)
PMCID: PMC2223289   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.01404-07   (Journal Full-text)

The transforming growth factor beta (TGFbeta) family has critical roles in the regulation of fertility. In addition, the pathogenesis of some human cancers is attributed to misregulation of TGFbeta function and SMAD2 or SMAD4 mutations. There are limited mouse models for the BMP signaling SMADs (BR-SMADs) 1, 5, and 8 because of embryonic lethality and suspected genetic redundancy. Using tissue-specific ablation in mice, we deleted the BR-SMADs from somatic cells of ovaries and testes. Single conditional knockouts for Smad1 or Smad5 or mice homozygous null for Smad8 are viable and fertile. Female double Smad1 Smad5 and triple Smad1 Smad5 Smad8 conditional knockout mice become infertile and develop metastatic granulosa cell tumors. Male double Smad1 Smad5 conditional knockout mice are fertile but demonstrate metastatic testicular tumor development. Microarray analysis indicated significant alterations in expression of genes related to the TGFbeta pathway, as well as genes involved in infertility and extracellular matrix production. These data strongly implicate the BR-SMADs as part of a critical developmental pathway in ovaries and testis that, when disrupted, leads to malignant transformation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  

Objects Annotated

Genes (Rattus norvegicus)
Smad1  (SMAD family member 1)
Smad5  (SMAD family member 5)

Genes (Mus musculus)
Smad1  (SMAD family member 1)
Smad5  (SMAD family member 5)

Genes (Homo sapiens)
SMAD1  (SMAD family member 1)
SMAD5  (SMAD family member 5)


Additional Information