Breeding protocol 57BL/6J-ApcMin/J mice
Our gastrointestinal tract (including small intestine and colon) is in contact with nutrients, metabolites and resident bacteria. This interaction is fundamental for our health but also induces constant damage to the lining of the intestine (epithelium). Therefore this epithelium needs to be constantly renewed. In fact, its complete renewal occurs every 3-5 days, and is achieved by a population of adult stem cells that continuously divide and give rise to the rest of epithelial cells (1). This proliferation and differentiation process is finely controlled by a network of signaling pathways that when deregulated lead to malignant transformation (2). This fact is reflected in the number of gastrointestinal cancers worldwide. For example, colorectal cancer is the 4th most frequent reason for cancer associated death worldwide, accounting for around 700.000 victims a year, which makes a medical necessity to understand the underlying mechanisms regulating stem cell regulation and intestinal tumor development (3).
So, we plan to address the study of tumor development in the small intestine and the colon using a mouse model (ApcMin) that develops tumors due to unbalanced proliferation signaling on stem cells. These mice will be crossed to other mouse models deficient for our proteins of interest that will allow us to decipher the role of both proteins on tumor development and evolution.
Previous preliminary data of our lab suggest that these proteins can contribute to stem cell regulation and intestinal renewal, making them a possible part of the signaling network important to maintain homeostasis and that could be unbalanced during tumorigenesis.
ApcMin mouse is a frequently used mouse model to study tumor development affecting the intestine. These mice carry an heterozygous mutation (Apc Min/+) in the tumor suppressor gene Apc. As a consequence ApcMin mice are predisposed to small intestinal polyps development (approximately 30 small intestinal polyps), that only occasionally progress to invasive adenocarcinoma (4). We will use 400 mice for this breeding protocol.
Unfortunately, there are currently no alternatives to animals to analyze the factors that regulate intestinal tumor development. Since carcinogenesis is a complex, multifactorial process that is regulated by different cell types in constant communication with the environment, it is currently not possible to model this in vitro. Anyway we will strive to reduce the number of animals required for breeding as much as possible.
Also we cannot avoid a certain amount of distress in these mice associated to tumor development in the intestine. However, we will closely monitor these animals to prevent unnecessary suffering and apply the human endpoint procedures when needed.
(1)Barker et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007
(2)Barker et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature letters. 2009
(3)Gandomani, et al. Colorectal cancer in the world: incidence, mortality and risk factors. Biomed. Res. Therapy. 2017
(4)Yamada, Mori. Multistep carcinogenesis of the colon in Apc(Min/+) mouse. Cancer Sci. 2007
So, we plan to address the study of tumor development in the small intestine and the colon using a mouse model (ApcMin) that develops tumors due to unbalanced proliferation signaling on stem cells. These mice will be crossed to other mouse models deficient for our proteins of interest that will allow us to decipher the role of both proteins on tumor development and evolution.
Previous preliminary data of our lab suggest that these proteins can contribute to stem cell regulation and intestinal renewal, making them a possible part of the signaling network important to maintain homeostasis and that could be unbalanced during tumorigenesis.
ApcMin mouse is a frequently used mouse model to study tumor development affecting the intestine. These mice carry an heterozygous mutation (Apc Min/+) in the tumor suppressor gene Apc. As a consequence ApcMin mice are predisposed to small intestinal polyps development (approximately 30 small intestinal polyps), that only occasionally progress to invasive adenocarcinoma (4). We will use 400 mice for this breeding protocol.
Unfortunately, there are currently no alternatives to animals to analyze the factors that regulate intestinal tumor development. Since carcinogenesis is a complex, multifactorial process that is regulated by different cell types in constant communication with the environment, it is currently not possible to model this in vitro. Anyway we will strive to reduce the number of animals required for breeding as much as possible.
Also we cannot avoid a certain amount of distress in these mice associated to tumor development in the intestine. However, we will closely monitor these animals to prevent unnecessary suffering and apply the human endpoint procedures when needed.
(1)Barker et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 2007
(2)Barker et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature letters. 2009
(3)Gandomani, et al. Colorectal cancer in the world: incidence, mortality and risk factors. Biomed. Res. Therapy. 2017
(4)Yamada, Mori. Multistep carcinogenesis of the colon in Apc(Min/+) mouse. Cancer Sci. 2007