Reference SummarySerrano M, Cell 1996 Apr 5;85(1):27-37

Title

 Role of the INK4a locus in tumor suppression and cell mortality.

Authors

 Serrano M; Lee H; Chin L; Cordon-Cardo C; Beach D; DePinho RA

Journal

 Cell

Volume

 85

Issue

 1

Year

 1996

Pages

 27-37

Abstract

 The cell cycle inhibitor p16INK4a is inactivated in many human tumors and in families with hereditary melanoma and pancreatic cancer. Tumor-associated alterations in the INK4a locus may also affect the overlapping gene encoding p19ARF and the adjacent gene encoding p15I1NK4b, both negative regulators of cell proliferation. We report the phenotype of mice carrying a targeted deletion of the INK4a locus that eliminates both p16INK4a and p19ARF. The mice are viable but develop spontaneous tumors at an early age and are highly sensitive to carcinogenic treatments. INK4a-deficient primary fibroblasts proliferate rapidly and have a high colony-formation efficiency. In contrast with normal cells, the introduction of activated Ha-ras into INK4a-deficient fibroblasts can result in neoplastic transformation. These findings directly demonstrate that the INK4a locus functions to suppress neoplastic growth.

Links

 J:53805 – MGI References
8620534 – National Library of Medicine/PubMed

Strain Notes

Strain Note
STOCK These mice were generated using the WW6 ES cell line (75% 129/Sv, 20% C57BL/6, 5% SJL). Chimeric males were mated to C57BL/6 females. Offspring were then intercrossed to generate mice wild type, heterozygous, and homozygous for the mutant allele.
Wild type controls.
STOCK Cdkn2atm1Rdp These mice were generated using the WW6 ES cell line (75% 129/Sv, 20% C57BL/6, 5% SJL). Chimeric males were mated to C57BL/6 females. Offspring were then intercrossed to generate mice wild type, heterozygous, and homozygous for the mutant allele.
STOCK Cdkn2atm1Rdp/+ These mice were generated using the WW6 ES cell line (75% 129/Sv, 20% C57BL/6, 5% SJL). Chimeric males were mated to C57BL/6 females. Offspring were then intercrossed to generate mice wild type, heterozygous, and homozygous for the mutant allele.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
STOCK Cdkn2atm1Rdp Adipose tissue liposarcoma Adipose tissue

observed
STOCK Cdkn2atm1Rdp Blood vessel hemangiosarcoma Blood vessel

observed
STOCK Cdkn2atm1Rdp Connective tissue - Fibroblast fibrosarcoma Connective tissue - Fibroblast

observed
STOCK Cdkn2atm1Rdp Connective tissue - Fibroblast fibrosarcoma
  • ultraviolet-B radiation (UVB)
 Connective tissue - Fibroblast

observed
STOCK Cdkn2atm1Rdp Connective tissue - Fibroblast fibrosarcoma
  • ultraviolet-B radiation (UVB)
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Connective tissue - Fibroblast

observed
STOCK Cdkn2atm1Rdp Connective tissue - Fibroblast fibrosarcoma
  • ultraviolet-B radiation (UVB)
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Connective tissue - Fibroblast

observed
STOCK Cdkn2atm1Rdp/+ Connective tissue - Fibroblast fibrosarcoma
  • ultraviolet-B radiation (UVB)
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Connective tissue - Fibroblast

observed
STOCK Cdkn2atm1Rdp Leukocyte - Lymphocyte - B-lymphocyte lymphoma
  • ultraviolet-B radiation (UVB)
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Leukocyte - Lymphocyte - B-lymphocyte

observed
STOCK Cdkn2atm1Rdp Leukocyte - Lymphocyte - B-lymphocyte lymphoma Leukocyte - Lymphocyte - B-lymphocyte

observed
STOCK Cdkn2atm1Rdp Leukocyte lymphoma Leukocyte

observed
STOCK Cdkn2atm1Rdp Leukocyte lymphoma
  • ultraviolet-B radiation (UVB)
 Leukocyte

observed
STOCK Cdkn2atm1Rdp Leukocyte lymphoma
  • ultraviolet-B radiation (UVB)
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Leukocyte

observed
STOCK Cdkn2atm1Rdp/+ Leukocyte lymphoma
  • ultraviolet-B radiation (UVB)
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Leukocyte

observed
STOCK Cdkn2atm1Rdp Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

observed
STOCK Cdkn2atm1Rdp Mesodermal cell/mesoblast sarcoma
  • ultraviolet-B radiation (UVB)
 Mesodermal cell/mesoblast

observed
STOCK Cdkn2atm1Rdp Skin squamous cell carcinoma
  • ultraviolet-B radiation (UVB)
 Skin

observed
STOCK Cdkn2atm1Rdp Skin squamous cell carcinoma
  • ultraviolet-B radiation (UVB)
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Skin

observed
STOCK Cdkn2atm1Rdp/+ Skin squamous cell carcinoma
  • ultraviolet-B radiation (UVB)
  • 9,10-dimethyl-1,2-benzanthracene (DMBA)
 Skin

observed
C57BL/6 +/+ : STOCK Cdkn2atm1Rdp/+ Testis - Germ cell teratoma Testis - Germ cell

observed
STOCK (Unspecified organ) tumor (Unspecified organ)

0
STOCK Cdkn2atm1Rdp/+ (Unspecified organ) tumor (Unspecified organ)

0