User:Kabolmaali

Animal models for colorectal cancer
In recent years, there has been a scientific interest in developing animal models for various diseases and colorectal cancer (CRC) - being the second most common cancer - is not an exception. The models for colorectal cancer has been developped from the hereditary forms of familial colerectal cancer which is normally seen in human being. However, these models are not a true representative of CRC and there are some dissimilarities, for which newer models are being tested everyday.

familial adenomatous polyposis models
CRC models can be divided categorised on the type of animal, which develps CRC. Historically, Mouse models have been developed in 1990 and those are, by far, the most widely used models. ApcMin/+ which is based on a mutatin in Apc gene located on chromosome 5 is the first model described in 1990. This model has many advantages, including similar mutation basis as human being, development of multiple adenomatous polyps in the gut in a predictable manner, and being widely tested worldwide in different studies. However, there are some major drawbacks, limiting their use as a CRC model. First, the distribution of tumors are mainly limited to small intestine rather than colon, which is a major difference with the human trait. the colon:small intestine ratio of adenomtous polyps in standard ApcMin/+ is 1:40. Secondly, they rarely develop adenocarcinoma. The reason maybe due to the fact that these mice usually become moribund before they have the chance to develop carcinomatous transformation. ApcMin/+ can be based on different mutations. The standard ApcMin/+ - which has been described above- bears a mutation in codon 850 in Apc gene. Other variants, which will also have different phenotypes, include mutations in codon 716, 1309 and 1638. In order to improve the characteristics of these models, they have been crossed with other species with mutations in Wnt signalling pathway or TGF-beta. however, the amount of data available on these models are still limited.

Hereditary Non-Polyposis Colorectal Cancer models
These models are based on the mutations in Mlh1 or Msh2 genes. Although these models do not develop adenomtous polyps as the Min mice do, but they show a higher incidence of carcinomatous changes. In general, 90 percent of tumors in Mlh1 knockout mice will show invasive adenocarcinoma;however, only one third of them develop a tumor.

Pirc rat models
Polyposis in the rat colon kindred is the rat model of FAP. The mutation in this model is located in Apc gene as well - similar to Min mice. These model has several advantages to Min mice in terms of smiliarity to human disease. First of all, the distribution of adenomatous polyps are more similar to the human disease. There is some evidence that the tumor first appears in the colon and then in small intestine and the colon:small intestine ratio of polyps is 1:1. The second advantage is that the rat model lives longer than the mice model and therefore can be considered a better model for pharmacological trials. However, there is not much data available on this model currently.