Phenotypes Associated with This Genotype

Genotype
MGI:3774767

• Allelic Composition: Cdkn2a^tm1Cjs/Cdkn2a^tm1Cjs
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * NIH/OlaHsd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Metastasis of primary squamous cell carcinoma to lymph nodes and lungs in Cdkn2a^tm1Cjs/Cdkn2a^tm1Cjs mice

neoplasm

increased incidence of tumors by chemical induction ( J:93298 )

• by 20 weeks after a single dose of DMBA and twice weekly application of TPA for 15 weeks, mutants show an increase in papilloma number and size compared to wild-type

increased metastatic potential ( J:93298 )

• mutants treated with DMBA/TPA exhibit increased dissemination of squamous cell carcinomas to lymph nodes and lungs compared to wild-type

increased tumor growth/size ( J:93298 )

• by 28 weeks after DMBA/TPA treatment, 33% of papillomas are greater than 8 mm vs. 14% from wild-type and can measure up to 16 mm in diameter which is never seen in wild-type

increased carcinoma incidence ( J:93298 )

• rate of malignant conversion from papillomas to carcinomas is accelerated in mutants treated with DMBA/TPA, with carcinomas developing as early as 14 weeks after initiation, compared to 22 weeks in wild-type

• by 28 weeks, 100% of mutants treated with DMBA/TPA develop carcinomas compared to 25% of wild-type

increased squamous cell carcinoma incidence ( J:93298 )

• mutants treated with DMBA/TPA to induce tumors exhibit increased dissemination and establishment of squamous cell carcinomas to lymph nodes and lungs compared to treated wild-type mice

increased papilloma incidence ( J:93298 )

• mutants have an average of 2.97 more papillomas than wild-type after DMBA/TPA treatment

• all papillomas contain an AT transversion at codon 61 of Hras, resulting in a constitutively activated Ras protein, and reduced expression of Trp53

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:93298 )

• by 20 weeks after a single dose of DMBA and twice weekly application of TPA for 15 weeks, mutants show an increase in papilloma number and size compared to wild-type