Reference SummaryKucherlapati MH, Proc Natl Acad Sci U S A 2008 Oct 7;105(40):15493-8

Title

Loss of Rb1 in the gastrointestinal tract of Apc1638N mice promotes tumors of the cecum and proximal colon.

Authors

Kucherlapati MH; Yang K; Fan K; Kuraguchi M; Sonkin D; Rosulek A; Lipkin M; Bronson RT; Aronow BJ; Kucherlapati R

Journal

Proc Natl Acad Sci U S A

Volume

105

Issue

40

Year

2008

Pages

15493-8

Abstract

To examine the role of Rb1 in gastrointestinal (GI) tumors, we generated mice with an Apc(1638N) allele, Rb(tm2brn) floxed alleles, and a villin-cre transgene (RBVCA). These animals had exon 19 deleted from Rb1 throughout the GI tract. We have shown previously that Rb1 deficiency is insufficient for GI tumor initiation, with inactivation of an Apc allele capable of overcoming the insufficiency. In this study we demonstrate that RBVCA mice have reduced median survival because of an increase in tumor incidence and multiplicity in the cecum and the proximal colon. Large intestinal tumors are predominantly adenomas, whereas the tumors of the small intestine are a mixture of adenomas and adenocarcinomas. We find truncation mutations to the second Apc allele in tumors of both the large and small intestine. Expression profiles of duodenal and cecal tumors relative to each other show unique gene subsets up and down regulated. Substantial expression patterns compare to human colorectal cancer, including recapitulation of embryonic genes. Our results indicate that Rb1 has significant influence over tumor location in the GI tract, and that both cecal and duodenal tumors initiate through inactivation of Apc. Expression profile analysis indicates the two tumor types differentially regulate distinct sets of genes that are over-expressed in a majority of human colorectal carcinomas.

Links

J:143449 – Mouse Genome Informatics
18832169 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
STOCK Tg(Vil1-cre)20Syr Gastrointestinal tract adenocarcinoma Gastrointestinal tract

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Gastrointestinal tract adenocarcinoma Gastrointestinal tract

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Gastrointestinal tract adenocarcinoma Gastrointestinal tract

33.33

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Gastrointestinal tract adenocarcinoma Gastrointestinal tract

46.67

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Gastrointestinal tract adenocarcinoma Gastrointestinal tract

0

STOCK Apctm1Rak Rb1tm2Brn/+ Gastrointestinal tract adenocarcinoma Gastrointestinal tract

33.33

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Gastrointestinal tract adenocarcinoma Gastrointestinal tract

16.67

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Gastrointestinal tract adenocarcinoma Gastrointestinal tract

50

STOCK Tg(Vil1-cre)20Syr Gastrointestinal tract adenoma - villous Gastrointestinal tract

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Gastrointestinal tract adenoma - villous Gastrointestinal tract

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Gastrointestinal tract adenoma - villous Gastrointestinal tract

33.33

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Gastrointestinal tract adenoma - villous Gastrointestinal tract

6.67

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Gastrointestinal tract adenoma - villous Gastrointestinal tract

0

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Gastrointestinal tract adenoma - villous Gastrointestinal tract

0

STOCK Apctm1Rak Rb1tm2Brn/+ Gastrointestinal tract adenoma - villous Gastrointestinal tract

22.22

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Gastrointestinal tract adenoma - villous Gastrointestinal tract

16.67

STOCK Tg(Vil1-cre)20Syr Gastrointestinal tract tumor Gastrointestinal tract

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Gastrointestinal tract tumor Gastrointestinal tract

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Gastrointestinal tract tumor Gastrointestinal tract

100

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Gastrointestinal tract tumor Gastrointestinal tract

100

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Gastrointestinal tract tumor Gastrointestinal tract

100

STOCK Apctm1Rak Rb1tm2Brn/+ Gastrointestinal tract tumor Gastrointestinal tract

88.89

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Gastrointestinal tract tumor Gastrointestinal tract

100

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Gastrointestinal tract tumor Gastrointestinal tract

88.89

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine - Cecum adenoma - villous Intestine - Large Intestine - Cecum

observed

STOCK Tg(Vil1-cre)20Syr Intestine - Large Intestine - Cecum tumor Intestine - Large Intestine - Cecum

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine - Cecum tumor Intestine - Large Intestine - Cecum

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine - Cecum tumor Intestine - Large Intestine - Cecum

86.67

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine - Cecum tumor Intestine - Large Intestine - Cecum

73.33

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine - Cecum tumor Intestine - Large Intestine - Cecum

20

STOCK Apctm1Rak Rb1tm2Brn/+ Intestine - Large Intestine - Cecum tumor Intestine - Large Intestine - Cecum

88.89

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine - Cecum tumor Intestine - Large Intestine - Cecum

0

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Intestine - Large Intestine - Cecum tumor Intestine - Large Intestine - Cecum

5.56

STOCK Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Distal tumor Intestine - Large Intestine - Colon - Distal

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Distal tumor Intestine - Large Intestine - Colon - Distal

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Distal tumor Intestine - Large Intestine - Colon - Distal

6.67

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Distal tumor Intestine - Large Intestine - Colon - Distal

6.67

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Distal tumor Intestine - Large Intestine - Colon - Distal

0

STOCK Apctm1Rak Rb1tm2Brn/+ Intestine - Large Intestine - Colon - Distal tumor Intestine - Large Intestine - Colon - Distal

22.22

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Distal tumor Intestine - Large Intestine - Colon - Distal

0

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Distal tumor Intestine - Large Intestine - Colon - Distal

0

STOCK Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Proximal tumor Intestine - Large Intestine - Colon - Proximal

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Proximal tumor Intestine - Large Intestine - Colon - Proximal

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Proximal tumor Intestine - Large Intestine - Colon - Proximal

26.67

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Proximal tumor Intestine - Large Intestine - Colon - Proximal

6.67

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Proximal tumor Intestine - Large Intestine - Colon - Proximal

0

STOCK Apctm1Rak Rb1tm2Brn/+ Intestine - Large Intestine - Colon - Proximal tumor Intestine - Large Intestine - Colon - Proximal

0

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Proximal tumor Intestine - Large Intestine - Colon - Proximal

0

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Intestine - Large Intestine - Colon - Proximal tumor Intestine - Large Intestine - Colon - Proximal

0

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0

STOCK Tg(Vil1-cre)20Syr Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

13.33

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0

STOCK Apctm1Rak Rb1tm2Brn/+ Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine adenocarcinoma Intestine - Large Intestine

0

STOCK Tg(Vil1-cre)20Syr Intestine - Large Intestine adenoma - villous Intestine - Large Intestine

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine adenoma - villous Intestine - Large Intestine

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine adenoma - villous Intestine - Large Intestine

6.67

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine adenoma - villous Intestine - Large Intestine

0

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Intestine - Large Intestine adenoma - villous Intestine - Large Intestine

0

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine adenoma - villous Intestine - Large Intestine

0

STOCK Apctm1Rak Rb1tm2Brn/+ Intestine - Large Intestine adenoma - villous Intestine - Large Intestine

11.11

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine adenoma - villous Intestine - Large Intestine

0

STOCK Tg(Vil1-cre)20Syr Intestine - Large Intestine tumor Intestine - Large Intestine

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine tumor Intestine - Large Intestine

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Large Intestine tumor Intestine - Large Intestine

86.67

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine tumor Intestine - Large Intestine

73.33

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine tumor Intestine - Large Intestine

20

STOCK Apctm1Rak Rb1tm2Brn/+ Intestine - Large Intestine tumor Intestine - Large Intestine

22.22

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Large Intestine tumor Intestine - Large Intestine

0

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Intestine - Large Intestine tumor Intestine - Large Intestine

5.56

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

50

STOCK Tg(Vil1-cre)20Syr Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

33.33

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

33.33

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

0

STOCK Apctm1Rak Rb1tm2Brn/+ Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

33.33

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

16.67

STOCK Tg(Vil1-cre)20Syr Intestine - Small Intestine adenoma - villous Intestine - Small Intestine

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Small Intestine adenoma - villous Intestine - Small Intestine

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Small Intestine adenoma - villous Intestine - Small Intestine

26.67

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Intestine - Small Intestine adenoma - villous Intestine - Small Intestine

6.67

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Intestine - Small Intestine adenoma - villous Intestine - Small Intestine

0

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Small Intestine adenoma - villous Intestine - Small Intestine

0

STOCK Apctm1Rak Rb1tm2Brn/+ Intestine - Small Intestine adenoma - villous Intestine - Small Intestine

11.11

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Small Intestine adenoma - villous Intestine - Small Intestine

16.67

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Small Intestine polyp Intestine - Small Intestine

observed

STOCK Tg(Vil1-cre)20Syr Intestine - Small Intestine polyp Intestine - Small Intestine

observed

STOCK Tg(Vil1-cre)20Syr Intestine - Small Intestine tumor Intestine - Small Intestine

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Small Intestine tumor Intestine - Small Intestine

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Intestine - Small Intestine tumor Intestine - Small Intestine

100

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Intestine - Small Intestine tumor Intestine - Small Intestine

93.33

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Small Intestine tumor Intestine - Small Intestine

100

STOCK Apctm1Rak Rb1tm2Brn/+ Intestine - Small Intestine tumor Intestine - Small Intestine

88.89

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Intestine - Small Intestine tumor Intestine - Small Intestine

100

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Intestine - Small Intestine tumor Intestine - Small Intestine

88.89

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Pituitary gland tumor Pituitary gland

observed

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Pituitary gland tumor Pituitary gland

observed

STOCK Tg(Vil1-cre)20Syr Stomach tumor Stomach

0

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Stomach tumor Stomach

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Stomach tumor Stomach

26.67

STOCK Apctm1Rak/+ Rb1tm2Brn/+ Tg(Vil1-cre)20Syr Stomach tumor Stomach

86.67

STOCK Apctm1Rak/+ Tg(Vil1-cre)20Syr Stomach tumor Stomach

40

STOCK Apctm1Rak Rb1tm2Brn/+ Stomach tumor Stomach

44.44

C57BL/6-Apctm1Rak/+ Tg(Vil1-cre)20Syr Stomach tumor Stomach

33.33

STOCK Msh2tm2.1Rak Tg(Vil1-cre)20Syr Stomach tumor Stomach

0

STOCK Apctm1Rak/+ Rb1tm2Brn Tg(Vil1-cre)20Syr Thyroid gland - Medulla - C cell tumor Thyroid gland - Medulla - C cell

observed

STOCK Rb1tm2Brn Tg(Vil1-cre)20Syr Thyroid gland tumor Thyroid gland

observed