Phenotypes associated with this allele

• Allele Symbol: Kras^tm2Bbd
• Allele Name: targeted mutation 2, Mariano Barbacid
• Allele ID: MGI:4844115
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Cdk2^tm2Sgo/Cdk2^tm2Sgo Kras^tm1Bbd/Kras^tm2Bbd Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844189
cn2	Kras^tm1Bbd/Kras^tm2Bbd Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844190
cn3	Cdk4^tm2.1Bbd/Cdk4^tm2.1Bbd Kras^tm1Bbd/Kras^tm2Bbd Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844191
cn4	Cdk4^tm2.2Bbd/Cdk4^tm2.1Bbd Kras^tm1Bbd/Kras^tm2Bbd Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844192

Genotype
MGI:4844189

cn1

• Allelic Composition: Cdk2^tm2Sgo/Cdk2^tm2Sgo; Kras^tm1Bbd/Kras^tm2Bbd; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

premature death ( J:161780 )

• tamoxifen-treated mice exhibit an increase in lifespan compared with similarly treated Kras^tm1Bbd/Kras⁺ Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} littermates

neoplasm

decreased tumor incidence ( J:161780 )

• tamoxifen-treated mice exhibit reduced tumor burden and tumor grade compared with similarly treated Kras^tm1Bbd/Kras⁺ Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

Genotype
MGI:4844190

cn2

• Allelic Composition: Kras^tm1Bbd/Kras^tm2Bbd; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:161780 )

• 50% survival for tamoxifen-treated mice is 25 weeks compared with 42 weeks for similarly treated Kras^tm1Bbd/Kras⁺ Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} littermates

neoplasm

increased lung tumor incidence ( J:161780 )

• lung tumors in tamoxifen-treated mice are more aggressive than in similarly treated Kras^tm1Bbd/Kras⁺ Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

• however, treatment with the Cdk4 inhibitor PD0332991 reduces tumor formation

increased lung non-small cell carcinoma incidence ( J:161780 )

• in mice treated with tamoxifen

cellular

increased cell proliferation ( J:161780 )

• proliferation of lung cells in tamoxifen-treated mice exhibit 8- to 10-fold greater proliferation than in Cdk4^tm2.1Bbd/Cdk4^tm2.1Bbd Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

respiratory system

increased lung tumor incidence ( J:161780 )

• lung tumors in tamoxifen-treated mice are more aggressive than in similarly treated Kras^tm1Bbd/Kras⁺ Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

• however, treatment with the Cdk4 inhibitor PD0332991 reduces tumor formation

increased lung non-small cell carcinoma incidence ( J:161780 )

• in mice treated with tamoxifen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lung cancer		DOID:1324	OMIM:211980 OMIM:608935 OMIM:612571 OMIM:612593 OMIM:614210	J:161780

Genotype
MGI:4844191

cn3

• Allelic Composition: Cdk4^tm2.1Bbd/Cdk4^tm2.1Bbd; Kras^tm1Bbd/Kras^tm2Bbd; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

neoplasm

decreased tumor growth/size ( J:161780 )

• lung cells in tamoxifen-treated mice exhibit 8- to 10-fold reduction in proliferation and early senescence compared to in similarly treated Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

increased adenocarcinoma incidence ( J:161780 )

• tamoxifen-treated mice exhibit adenocarcinomas that are not as severe as in Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

cellular

decreased cell proliferation ( J:161780 )

• proliferation of lung cells in tamoxifen-treated mice exhibit 8- to 10-fold less proliferation than in similarly treated Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

early cellular replicative senescence ( J:161780 )

• tamoxifen-treated mice exhibit increased cell replicative senescence in the lungs compared to in similarly treated Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

Genotype
MGI:4844192

cn4

• Allelic Composition: Cdk4^tm2.2Bbd/Cdk4^tm2.1Bbd; Kras^tm1Bbd/Kras^tm2Bbd; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

neoplasm

decreased tumor growth/size ( J:161780 )

• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit decreased proliferation and early senescence of tumor cells compared with tamoxifen and infected with GFP-expressing adenovirus

decreased tumor incidence ( J:161780 )

• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit reduced lesions compared to in mice treated with tamoxifen and infected with GFP-expressing adenovirus

increased tumor incidence ( J:161780 )

• in tamoxifen-treated mice as in similarly treated Kras^tm1Bbd/Kras^tm2Bbd Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} mice

cellular

decreased cell proliferation ( J:161780 )

• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit early senescence of tumor cells compared with tamoxifen and infected with GFP-expressing adenovirus

early cellular replicative senescence ( J:161780 )

• tamoxifen-treated mice infected with a flp-expressing adenovirus exhibit decreased proliferation of tumor cells compared with tamoxifen and infected with GFP-expressing adenovirus