Smad4 CKO Mouse Model


Smad4 was originally discovered in pancreatic cancer and is also known as Deleted in Pancreatic Carcinoma Locus 4 (DPC4). Smad4 is an important marker for the diagnosis of pancreatic cancer, with the rate of its deletion and mutation being 50% in pancreatic cancer. Smad4 is deleted or mutated in a wide range of tumors, especially in the tumors of the digestive system. Smad4 plays the role of a tumor suppressor and is closely related to tumor invasion, distant metastasis, and the TNM staging of the International Union Against Cancer (UICC). Through the transforming growth factor β (TGFβ) and bone morphogenic protein (BMP) signaling pathways, Smad4 transmits signals from the cell surface to the nucleus and is involved in the growth control and transcriptional regulation during development.


Before gastrulation, the homozygous mice with systemic Smad4 knockout exhibit fatal damages to the extraembryonic blastoderm and endoderm. The heterozygous mice with systemic Smad4 knockout develop glandular and duodenal polyps.

 

Our own-developed Smad4 conditional knockout mice (Smad4-CKO) can be used to study cell proliferation and tumor suppression.


For example, after mating with mice carrying pancreas-specific Cre expression, Smad4-CKO mice can be used to study pancreatic duct abnormalities and pancreatic cancer.


smad4

Fig1. SMAD4 inactivation promotes transition to malignancy in colon cancer.(Cancer Res. 2011 Feb 1;71(3):998-1008. )


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