Phenotypes associated with this allele

• Allele Symbol: Kras^tm1Bbd
• Allele Name: targeted mutation 1, Mariano Barbacid
• Allele ID: MGI:3582830
• Summary: 31 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Kras^tm1Bbd/Kras^tm1Bbd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3582834
cn2	Kras^tm1Bbd/Kras^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5508232
cn3	Braf^tm1Sva/Braf^tm1Sva Kras^tm1Bbd/Kras^+ Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd Raf1^tm2Bacc/Raf1^tm2Bacc	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5508357
cn4	Kras^tm1Bbd/Kras^+ Raf1^tm2Bacc/Raf1^tm2Bacc	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5508337
cn5	Kras^tm1Bbd/Kras^+ Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd Raf1^tm2Bacc/Raf1^tm2Bacc	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:5508355
cn6	Kras^tm1Bbd/Kras^+ Trp53^tm1Brd/Trp53^+ Tg(Cela1-tTA)#Eps/? Tg(tetO-cre)3Jig/?	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * FVB/N	MGI:5502432
cn7	Braf^tm1Sva/Braf^tm1Sva Kras^tm1Bbd/Kras^+	involves: 129S1/Sv * 129X1/SvJ	MGI:5508329
cn8	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
cn9	Kras^tm1Bbd/Kras^+ Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844193
cn10	Cdk6^tm1Bbd/Cdk6^tm1Bbd Kras^tm1Bbd/Kras^+ Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844194
cn11	Cdk2^tm1Sgo/Cdk2^tm1Sgo Kras^tm1Bbd/Kras^+ Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844195
cn12	Kras^tm1Bbd/Kras^+ Mapk1^tm1.1Hed/Mapk1^tm1.1Hed	involves: 129S1/Sv * 129X1/SvJ	MGI:5508239
cn13	Braf^tm1Sva/Braf^tm1Sva Kras^tm1Bbd/Kras^+ Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:5508351
cn14	Kras^tm1Bbd/Kras^+ Map2k1^tm1Chrn/Map2k1^tm1Chrn	involves: 129S1/Sv * 129X1/SvJ	MGI:5508242
cn15	Cdk4^tm2.2Bbd/Cdk4^tm2.2Bbd Kras^tm1Bbd/Kras^tm1Bbd Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844188
cn16	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
cn17	Kras^tm1Bbd/Kras^tm2Bbd Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ	MGI:4844190
cn18	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
cn19	Cdk4^tm1.1Bbd/Cdk4^+ Kras^tm1Bbd/Kras^+ Tg(CMV-cre)1Cgn/?	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6	MGI:3582836
cn20	Kras^tm1Bbd/Kras^+ Tg(CMV-cre)1Cgn/?	involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6	MGI:3582835
cn21	Kras^tm1Bbd/Kras^+ Mapk14^tm2Nbr/Mapk14^+ Polr2a^tm1(cre/ERT2)Bbd/Polr2a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:3716857
cn22	Kras^tm1Bbd/Kras^+ Mapk14^tm1Nbr/Mapk14^tm2Nbr Polr2a^tm1(cre/ERT2)Bbd/Polr2a^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:3716855
cn23	Fntb^tm1Bbd/Fntb^tm1Bbd Kras^tm1Bbd/Kras^+ Polr2a^tm1(cre/ERT2)Bbd/Polr2a^tm1(cre/ERT2)Bbd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:3582832
cn24	Ctnnb1^tm1Mmt/Ctnnb1^+ Kras^tm1Bbd/Kras^+ Tg(Pbsn-cre)4Prb/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:3836578
cn25	Kras^tm1Bbd/Kras^+ Tg(Pbsn-cre)4Prb/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:3836577
cn26	Kras^tm1Bbd/Kras^+ Tg(CMV-cre/ERT)1Ipc/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:3582837
cn27	Kras^tm1Bbd/Kras^tm1Bbd Tg(Cela1-tTA)#Eps/? Tg(tetO-cre)3Jig/?	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5502430
cn28	Kras^tm1Bbd/Kras^+ Mapk1^tm1.1Hed/Mapk1^tm1.1Hed Mapk3^tm1Gpg/Mapk3^tm1Gpg	involves: 129/Sv * 129S1/Sv * 129X1/SvJ	MGI:5508240
cn29	Kras^tm1Bbd/Kras^+ Mapk3^tm1Gpg/Mapk3^tm1Gpg	involves: 129/Sv * 129S1/Sv * 129X1/SvJ	MGI:5508237
cn30	Kras^tm1Bbd/Kras^+ Map2k1^tm1Chrn/Map2k1^tm1Chrn Map2k2^tm1Chrn/Map2k2^tm1Chrn	involves: 129/Sv * 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL	MGI:5508244
cn31	Kras^tm1Bbd/Kras^+ Map2k2^tm1Chrn/Map2k2^tm1Chrn	involves: 129/Sv * 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL	MGI:5508243

Genotype
MGI:3582834

hm1

• Allelic Composition: Kras^tm1Bbd/Kras^tm1Bbd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:86101 )

• homozygous embryos die at midgestation similar to Kras^tm1Tyi

Genotype
MGI:5508232

cn2

• Allelic Composition: Kras^tm1Bbd/Kras⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

decreased survivor rate ( J:172200 )

• 50% survival at 40 weeks of age following intratracheal instillation of Ad-Cre

premature death ( J:172200 )

• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), 50% of mice die by 40 weeks

neoplasm

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre)

respiratory system

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre)

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:172200

Genotype
MGI:5508357

cn3

• Allelic Composition: Braf^tm1Sva/Braf^tm1Sva; Kras^tm1Bbd/Kras⁺; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}; Raf1^tm2Bacc/Raf1^tm2Bacc
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

cellular

decreased cell proliferation ( J:172200 )

• primary mouse embryonic fibroblasts exposed to 4OHT for 5 days to activate cre/ERT2 recombinase exhibit decreased proliferation that is similar to that in single Kras mutants without further additive effects

Genotype
MGI:5508337

cn4

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Raf1^tm2Bacc/Raf1^tm2Bacc
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:172200 )

• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mice show 50% survival at 63 weeks compared to 38 weeks in single Kras heterozygous controls, indicating an 83% increase in survival

neoplasm

decreased classified tumor incidence ( J:172200 )

• tumor burden is reduced compared to single Kras heterozygotes; tumors that are found express Raf1

Genotype
MGI:5508355

cn5

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}; Raf1^tm2Bacc/Raf1^tm2Bacc
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

cellular

decreased cell proliferation ( J:172200 )

• primary mouse embryonic fibroblasts exposed to 4OHT for 5 days to activate cre/ERT2 recombinase exhibit decreased proliferation compared to single Kras heterozygotes

Genotype
MGI:5502432

cn6

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Trp53^tm1Brd/Trp53⁺; Tg(Cela1-tTA)#Eps/?; Tg(tetO-cre)3Jig/?
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:119988 )

• 50% mortality by 6 months of age

• 100% mortality by 1 year of age

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:119988 )

• all mice develop moderately to poorly differentiated pancreatic ductal adenocarcinomas, peritoneal explants, and perineural extensions

increased metastatic potential ( J:119988 )

• metastases develop affecting liver, diaphragm, lungs, lymph nodes, and spleen

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:119988 )

• all mice develop moderately to poorly differentiated pancreatic ductal adenocarcinomas, peritoneal explants, and perineural extensions

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:119988

Genotype
MGI:5508329

cn7

• Allelic Composition: Braf^tm1Sva/Braf^tm1Sva; Kras^tm1Bbd/Kras⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:172200 )

• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mice show 50% survival at 41.5 weeks compared to 40 weeks in single Kras heterozygous controls, indicating similar survival

neoplasm

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes

respiratory system

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes

Genotype
MGI:4844192

cn8

• 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

Genotype
MGI:4844193

cn9

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

mortality/aging

premature death ( J:161780 )

• the mean lifespan of mice treated tamoxifen is 34-42 weeks

neoplasm

increased adenoma incidence ( J:161780 )

• in mice treated with tamoxifen at weaning

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

• in mice treated with tamoxifen at weaning

respiratory system

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

• in mice treated with tamoxifen at weaning

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:4844194

cn10

• Allelic Composition: Cdk6^tm1Bbd/Cdk6^tm1Bbd; Kras^tm1Bbd/Kras⁺; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:161780 )

• 50% of tamoxifen-treated mice survive at 40 weeks

neoplasm

increased adenoma incidence ( J:161780 )

• in mice treated with tamoxifen at weaning

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

• in mice treated with tamoxifen at weaning

respiratory system

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

• in mice treated with tamoxifen at weaning

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:4844195

cn11

• Allelic Composition: Cdk2^tm1Sgo/Cdk2^tm1Sgo; Kras^tm1Bbd/Kras⁺; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:161780 )

• mice treated tamoxifen at weaning exhibit an increase in lifespan of 8 weeks (42 weeks) compared with similarly treated Kras^tm1Bbd/Kras⁺ Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd} littermates (34 weeks)

neoplasm

decreased tumor incidence ( J:161780 )

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

Genotype
MGI:5508239

cn12

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Mapk1^tm1.1Hed/Mapk1^tm1.1Hed
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:172200 )

• 50% survival at 34.9 weeks versus 31.2 weeks in single Kras mutants following intratracheal instillation of Ad-Cre, indicating a 16% increase in survival

neoplasm

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes

respiratory system

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes

Genotype
MGI:5508351

cn13

• Allelic Composition: Braf^tm1Sva/Braf^tm1Sva; Kras^tm1Bbd/Kras⁺; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

cellular

decreased cell proliferation ( J:172200 )

• primary mouse embryonic fibroblasts exposed to 4OHT for 5 days to activate cre/ERT2 recombinase exhibit decreased proliferation compared to single Kras heterozygotes

Genotype
MGI:5508242

cn14

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Map2k1^tm1Chrn/Map2k1^tm1Chrn
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:172200 )

• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mutants show 50% survival at 44 weeks compared to 37.5 weeks in single Kras heterozygous controls, indicating a slight 22% increase in survival

neoplasm

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes

respiratory system

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes

Genotype
MGI:4844188

cn15

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

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:4844189

cn16

• 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

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

cn17

• 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

cn18

• 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:3582836

cn19

• Allelic Composition: Cdk4^tm1.1Bbd/Cdk4⁺; Kras^tm1Bbd/Kras⁺; Tg(CMV-cre)1Cgn/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6

neoplasm

increased pituitary adenoma incidence ( J:86101 )

increased lung adenoma incidence ( J:86101 )

• latency to develop lung adenomas is significantly shorter compared to double mutants wild-type for Cdk4; however development of tumors characteristic of Cdk4^tm1.1Bbd mutant mice is not accelerated

increased sarcoma incidence ( J:86101 )

• histiocytic sarcoma and other sarcomas are seen

increased hemangiosarcoma incidence ( J:86101 )

increased papilloma incidence ( J:86101 )

• anal papillomas are seen

digestive/alimentary system

abnormal pancreatic duct morphology ( J:86101 )

• focal metaplasia in the pancreatic ducts consisting of tall columnar cells with abundant apical mucin resembling gastric surface epithelial cells

endocrine/exocrine glands

abnormal pancreatic duct morphology ( J:86101 )

• focal metaplasia in the pancreatic ducts consisting of tall columnar cells with abundant apical mucin resembling gastric surface epithelial cells

increased pituitary adenoma incidence ( J:86101 )

nervous system

increased pituitary adenoma incidence ( J:86101 )

respiratory system

increased lung adenoma incidence ( J:86101 )

• latency to develop lung adenomas is significantly shorter compared to double mutants wild-type for Cdk4; however development of tumors characteristic of Cdk4^tm1.1Bbd mutant mice is not accelerated

Genotype
MGI:3582835

cn20

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Tg(CMV-cre)1Cgn/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * BALB/cJ * C57BL/6

mortality/aging

premature death ( J:86101 )

• double mutants develop breathing difficulties after 7 - 8 months of age

prenatal lethality, incomplete penetrance ( J:86101 )

• frequent embryonic lethality; however, a significant number of double mutants survive

neoplasm

increased lung adenoma incidence ( J:86101 )

• a large spectrum of multifocal lesions are seen in the lung including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes

increased lung adenocarcinoma incidence ( J:86101 )

• large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes

increased sarcoma incidence ( J:86101 )

• histiocytic sarcoma and other sarcomas seen in 2 out of 20 and 3 out of 20 double mutants, respectively

increased papilloma incidence ( J:86101 )

• anal papillomas seen in 3 out of 20 double mutants

cellular

abnormal cell proliferation ( J:86101 )

• MEFs expressing the oncogenic protein do not undergo proliferative senescence and proliferate continuously as immortal cells

respiratory system

increased lung adenoma incidence ( J:86101 )

• a large spectrum of multifocal lesions are seen in the lung including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes

increased lung adenocarcinoma incidence ( J:86101 )

• large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes

respiratory distress ( J:86101 )

• double mutants develop breathing difficulties after 7 - 8 months of age

Genotype
MGI:3716857

cn21

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Mapk14^tm2Nbr/Mapk14⁺; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

mortality/aging

premature death ( J:122397 )

• mice live up to 40 weeks

neoplasm

increased hemolymphoid system tumor incidence ( J:122397 )

• by 24 weeks, mice develop tumors in the thymus

increased lung tumor incidence ( J:122397 )

• by 24 weeks, mice develop tumors in lungs

increased lung adenoma incidence ( J:122397 )

• at 4 weeks after 5-hydroxytamoxifen treatment, a few small adenomas are observed in some animals

respiratory system

increased lung tumor incidence ( J:122397 )

• by 24 weeks, mice develop tumors in lungs

increased lung adenoma incidence ( J:122397 )

• at 4 weeks after 5-hydroxytamoxifen treatment, a few small adenomas are observed in some animals

Genotype
MGI:3716855

cn22

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Mapk14^tm1Nbr/Mapk14^tm2Nbr; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

mortality/aging

premature death ( J:122397 )

• mice die before week 32 due to increased lung cancer progression

respiratory system

enlarged lung ( J:122397 )

• 20 weeks after treatment, lungs are increased in size

increased lung tumor incidence ( J:122397 )

• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs

• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices

• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass

increased lung adenoma incidence ( J:122397 )

• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14^tm2Nbr/+ control mice

increased lung adenocarcinoma incidence ( J:122397 )

• adenocarcinomas are detected at 15 weeks but not in controls

abnormal lung development ( J:122397 )

• lung differentiation is abnormal with increased SP-C-positive cells

neoplasm

abnormal tumor incidence ( J:122397 )

• mice also have tumors in the thymus and organs such as kidney and liver by 24 weeks after treatment whereas controls only have tumors in lungs and thymus

increased lung tumor incidence ( J:122397 )

• 2 weeks after 5-hydroxytamoxifen treatment, small tumors are found in the lungs

• 20 weeks after treatment, lungs are oversized with 2-3 times as many tumors, many often >2mm in diameter, while lungs of Kras, Mapk14 heterozygotes have normal lungs with fewer, smaller tumors; tumors in Mapk14 homozygotes are more poorly differentiated and have higher mitotic indices

• at 26 weeks, total tumor number is slightly higher than in controls with much higher numbers of tumors larger than 2 mm in diameter and a higher ratio of lung mass to total mass

increased lung adenoma incidence ( J:122397 )

• tumors are detected 2 weeks after 5-hydroxytamoxifen treatment and after 4 weeks, clear signs of adenomas are present in most lungs compared to only a few small adenomas in lungs of treated Kras, Mapk14^tm2Nbr/+ control mice

increased lung adenocarcinoma incidence ( J:122397 )

• adenocarcinomas are detected at 15 weeks but not in controls

growth/size/body

enlarged lung ( J:122397 )

• 20 weeks after treatment, lungs are increased in size

Genotype
MGI:3582832

cn23

• Allelic Composition: Fntb^tm1Bbd/Fntb^tm1Bbd; Kras^tm1Bbd/Kras⁺; Polr2a^{tm1(cre/ERT2)Bbd}/Polr2a^{tm1(cre/ERT2)Bbd}
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

neoplasm

increased lung adenoma incidence ( J:98944 )

• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb

increased lung adenocarcinoma incidence ( J:98944 )

• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenocarcinomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb

respiratory system

increased lung adenoma incidence ( J:98944 )

• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb

increased lung adenocarcinoma incidence ( J:98944 )

• after treatment with 4-hydroxy-tamoxifen for 24 weeks multiple lung adenocarcinomas develop by 7 months of age; however no difference in the latency, number, or size of tumors was seen compared to double mutants wild-type for Fntb

Genotype
MGI:3836578

cn24

• Allelic Composition: Ctnnb1^tm1Mmt/Ctnnb1⁺; Kras^tm1Bbd/Kras⁺; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

mortality/aging

premature death ( J:143034 )

• mice die prior to day 300

reproductive system

squamous metaplasia of bulbourethral gland ( J:143034 )

♂ • mice exhibit keratinized squamous metaplasia in the bulbourethral gland unlike wild-type mice

increased prostate gland tumor incidence ( J:143034 )

♂ • all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice

neoplasm

increased prostate gland tumor incidence ( J:143034 )

♂ • all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice

renal/urinary system

squamous metaplasia of urethral gland ( J:143034 )

• mice exhibit keratinized squamous metaplasia in the urethral gland unlike wild-type mice

endocrine/exocrine glands

squamous metaplasia of bulbourethral gland ( J:143034 )

♂ • mice exhibit keratinized squamous metaplasia in the bulbourethral gland unlike wild-type mice

increased prostate gland tumor incidence ( J:143034 )

♂ • all mice develop diffuse, locally invasive carcinomas in the prostate that develop from solid or sheet-like proliferation with occasional rosette structures, nuclear atypia, apoptotic bodies, and mitosis unlike in wild-type mice

squamous metaplasia of urethral gland ( J:143034 )

• mice exhibit keratinized squamous metaplasia in the urethral gland unlike wild-type mice

Genotype
MGI:3836577

cn25

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

reproductive system

prostate gland hyperplasia ( J:143034 )

♂ • at 200 days, 100% of mice exhibit atypical hyperplasia unlike wild-type mice

♂ • at 500 days, 93% of mice exhibit atypical hyperplasia unlike wild-type mice

increased prostate gland adenocarcinoma incidence ( J:143034 )

♂ • in 7% of mice at 500 days

increased prostate intraepithelial neoplasia incidence ( J:143034 )

♂ • at 200 days, 67% of mice develop prostate intraepithelial neoplasia that display foci of small solid and cribiform intraluminal proliferation of atypical cells and nuclear atypia unlike wild-type mice

♂ • at 500 days, 60% of mice exhibit prostate intraepithelial neoplasia unlike in wild-type mice

neoplasm

increased prostate gland adenocarcinoma incidence ( J:143034 )

♂ • in 7% of mice at 500 days

increased prostate intraepithelial neoplasia incidence ( J:143034 )

♂ • at 200 days, 67% of mice develop prostate intraepithelial neoplasia that display foci of small solid and cribiform intraluminal proliferation of atypical cells and nuclear atypia unlike wild-type mice

♂ • at 500 days, 60% of mice exhibit prostate intraepithelial neoplasia unlike in wild-type mice

endocrine/exocrine glands

prostate gland hyperplasia ( J:143034 )

♂ • at 200 days, 100% of mice exhibit atypical hyperplasia unlike wild-type mice

♂ • at 500 days, 93% of mice exhibit atypical hyperplasia unlike wild-type mice

increased prostate gland adenocarcinoma incidence ( J:143034 )

♂ • in 7% of mice at 500 days

increased prostate intraepithelial neoplasia incidence ( J:143034 )

♂ • at 200 days, 67% of mice develop prostate intraepithelial neoplasia that display foci of small solid and cribiform intraluminal proliferation of atypical cells and nuclear atypia unlike wild-type mice

♂ • at 500 days, 60% of mice exhibit prostate intraepithelial neoplasia unlike in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:143034

Genotype
MGI:3582837

cn26

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Tg(CMV-cre/ERT)1Ipc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

mortality/aging

premature death ( J:86101 )

• double mutants treated with 4-hydroxy-tamoxifen at 10 days of age develop breathing difficulties after 7 - 8 months of age

neoplasm

increased lung adenoma incidence ( J:86101 )

• after treatment with 4-hydroxy-tamoxifen at 10 days of age, a large spectrum of multifocal lesions are seen in the lung at 7-8 months of age including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes

increased lung adenocarcinoma incidence ( J:86101 )

• after treatment with 4-hydroxy-tamoxifen at 10 days of age, at 7-8 months of age large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes are seen

cellular

abnormal fibroblast proliferation ( J:86101 )

• MEFs expressing the oncogenic protein do not undergo proliferative senescence and proliferate continuously as immortal cells

respiratory system

increased lung adenoma incidence ( J:86101 )

• after treatment with 4-hydroxy-tamoxifen at 10 days of age, a large spectrum of multifocal lesions are seen in the lung at 7-8 months of age including; small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas that compress adjacent lung structures and appear to derive from type II pneumocytes

increased lung adenocarcinoma incidence ( J:86101 )

• after treatment with 4-hydroxy-tamoxifen at 10 days of age, at 7-8 months of age large bronchiolo-alveolar adenocarcinomas that compress adjacent lung structures and appear to derive from type II pneumocytes are seen

respiratory distress ( J:86101 )

• double mutants treated with 4-hydroxy-tamoxifen at 10 days of age develop breathing difficulties after 7 - 8 months of age

endocrine/exocrine glands

Harderian gland hyperplasia ( J:86101 )

• hyperplastic Harderian gland seen in double mutants treated with 4-hydroxy-tamoxifen at 10 days of age

Genotype
MGI:5502430

cn27

• Allelic Composition: Kras^tm1Bbd/Kras^tm1Bbd; Tg(Cela1-tTA)#Eps/?; Tg(tetO-cre)3Jig/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:119988 )

• focal morphological lesions develop in acinar and centroacinar cells at 1-3 months

• acinar to ductal metaplasias develop

• some mice develop ductal adenocarcinomas by 12 months

• properties are similar to those in human patients

• sometimes areas of non malignant hyperplasia develop

increased tumor latency ( J:119988 )

• latency is increased if gene expression is delayed by maintaining exposure to doxycycline until 10 days of age

• if doxycycline exposure continues to 2 months of age, no pancreatic abnormalities develop

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:119988 )

• sometimes areas of non malignant hyperplasia develop

• focal morphological lesions develop in acinar and centroacinar cells at 1-3 months

• acinar to ductal metaplasias develop

• some mice develop ductal adenocarcinomas by 12 months

• properties are similar to those in human patients

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:119988

Genotype
MGI:5508240

cn28

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Mapk1^tm1.1Hed/Mapk1^tm1.1Hed; Mapk3^tm1Gpg/Mapk3^tm1Gpg
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:172200 )

• following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), mutants show 50% survival at 63 weeks versus 48 weeks in single Kras mutants, a 40% increase in survival

neoplasm

decreased classified tumor incidence ( J:172200 )

• 6 months following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), only a few tumors are observed; tumors that are found express normal levels of Mapk1

Genotype
MGI:5508237

cn29

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Mapk3^tm1Gpg/Mapk3^tm1Gpg
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:172200 )

• 50% survival at 46.3 weeks of age is seen following intratracheal instillation of Ad-Cre, a 20% increase in survival compared to single Kras mutants

neoplasm

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes

respiratory system

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes

Genotype
MGI:5508244

cn30

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Map2k1^tm1Chrn/Map2k1^tm1Chrn; Map2k2^tm1Chrn/Map2k2^tm1Chrn
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL

mortality/aging

premature death ( J:172200 )

• Ad-Cre treated mice show 50% survival at 57 weeks of age compared to 33 weeks of age in single Kras heterozygous controls, indicating an almost 100% increase in survival

neoplasm

decreased classified tumor incidence ( J:172200 )

• 6 months following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre), only a few tumors are observed; tumors that are present carry unrecombined Map2k1 alleles and express normal levels of Map2k1

Genotype
MGI:5508243

cn31

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Map2k2^tm1Chrn/Map2k2^tm1Chrn
• Genetic Background: involves: 129/Sv * 129S1/Sv * 129X1/SvJ * C57BL/6J * SJL

mortality/aging

premature death ( J:172200 )

• Ad-Cre treated mutants show 50% survival at 52 weeks compared to 45 weeks in single Kras heterozygous controls, indicating a slight 19% increase in survival

neoplasm

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes

respiratory system

increased lung non-small cell carcinoma incidence ( J:172200 )

• mice develop non-small cell lung carcinoma following intratracheal instillation of adenovirus expressing Cre-recombinase (Ad-Cre); tumor burden in similar to that seen in single Kras heterozygotes