Phenotypes associated with this allele

• Allele Symbol: Kras^tm2Tyj
• Allele Name: targeted mutation 2, Tyler Jacks
• Allele ID: MGI:2135928
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Kras^tm2Tyj/Kras^+	involves: 129S2/SvPas	MGI:3770518
ht2	Kras^tm2Tyj/Kras^+	involves: 129S2/SvPas * C57BL/6	MGI:3770515
cx3	Kras^tm2Tyj/Kras^+ Trp53^tm1Glo/Trp53^+	involves: 129S2/SvPas * 129S7/SvEvBrd	MGI:3814436
cx4	Kras^tm2Tyj/Kras^+ Trp53^tm1Tyj/Trp53^+	involves: 129S2/SvPas * C57BL/6	MGI:3770520
cx5	Dmtf1^tm1Cjs/Dmtf1^+ Kras^tm2Tyj/Kras^+	involves: 129S2/SvPas * C57BL/6	MGI:3770615
cx6	Dmtf1^tm1Cjs/Dmtf1^tm1Cjs Kras^tm2Tyj/Kras^+	involves: 129S2/SvPas * C57BL/6	MGI:3770616
cx7	Kras^tm2Tyj/Kras^+ Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6	MGI:3770519

Genotype
MGI:3770518

ht1

• Allelic Composition: Kras^tm2Tyj/Kras⁺
• Genetic Background: involves: 129S2/SvPas

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

mortality/aging

premature death ( J:68981 , J:129627 )

• Background Sensitivity: mean age at death is ~350 days on pure 129/Sv background compared to 300 days on mixed background (J:68981)

• average lifespan is 373 days (J:68981)

neoplasm

increased tumor incidence ( J:129627 )

• mice develop adenocarcinomas, adenomas, lymphomas, mesotheliomas, angiosarcomas, fibrosarcomas, squamous carcinomas, rectal mucinous adenocarcinomas, melanomas, and papillomas

increased lymphoma incidence ( J:129627 )

increased T cell derived lymphoma incidence ( J:68981 )

• Background Sensitivity: ~10% of animals develop thymic lymphoma; incidence is lower than on pure 129/Sv background

increased carcinoma incidence ( J:129627 )

increased lung adenocarcinoma incidence ( J:136369 )

• develop lung adenocarcinomas by 6-8 months of age

• treatment of mice with PX-866, a PI3K inhibitor, decreases lung lesion volume and multiplicity

increased squamous cell carcinoma incidence ( J:129627 )

increased sarcoma incidence ( J:129627 )

increased fibrosarcoma incidence ( J:129627 )

increased hemangiosarcoma incidence ( J:129627 )

increased mesothelioma incidence ( J:129627 )

• 4 of 48 mice develop mesothelioma with no occurrence of peritoneal mesothelioma

increased papilloma incidence ( J:129627 )

increased skin papilloma incidence ( J:68981 )

• Background Sensitivity: about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background

integument

increased skin papilloma incidence ( J:68981 )

• Background Sensitivity: about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background

respiratory system

increased lung adenocarcinoma incidence ( J:136369 )

• develop lung adenocarcinomas by 6-8 months of age

• treatment of mice with PX-866, a PI3K inhibitor, decreases lung lesion volume and multiplicity

abnormal bronchus morphology ( J:136369 )

• a subset of mutant terminal bronchi contain 4 to 7 bronchioalveolar stem cells (BASCs) compared to 3 of fewer in wild-type bronchi, indicating expansion of BASCs

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:68981 )

• Background Sensitivity: ~10% of animals develop thymic lymphoma; incidence is lower than on pure 129/Sv background

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:68981 , J:136369

Genotype
MGI:3770515

ht2

• Allelic Composition: Kras^tm2Tyj/Kras⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:68981 )

• Background Sensitivity: mean age at death is ~300 days

neoplasm

increased tumor incidence ( J:68981 )

• all animals at time of death/sacrifice have extensive tumor burden

increased T cell derived lymphoma incidence ( J:68981 )

• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~20% of animals)

increased skin papilloma incidence ( J:68981 )

• Background Sensitivity: animals are prone to skin papillomas (seen in ~25% of animals); tumors typically arising on ears and snout are predominantly pedunculated and show limited tendency to progress to squamous cell carcinoma

increased lung tumor incidence ( J:68981 )

• 100% of animals show multifocal tumors at time of death/sacrifice

• tumors are detectable at 1 week of age as small pleural nodules; multiplicity and size of tumors increases with age, and ultimately result in respiratory distress and death

• tumors range from mild hyperplasia/dysplasia to overt carcinoma; small lesions consist of hyperplastic alveolar epithelium

• in older mice, infrequent metastases to thoracic lymph nodes, the kidney and other visceral organs

increased lung adenoma incidence ( J:68981 )

• as lesions enlarge, they form small alveolar adenomas; some show areas of glandular differentiation

increased lung adenocarcinoma incidence ( J:68981 )

• 5-10% of tumors have features of well-differentiated human papillary adenocarcinoma

digestive/alimentary system

abnormal large intestine crypts of Lieberkuhn morphology ( J:68981 )

• mutants have multiple aberrant crypt foci (ACF) of the colon

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:68981 )

• mutants have multiple aberrant crypt foci (ACF) of the colon

increased T cell derived lymphoma incidence ( J:68981 )

• Background Sensitivity: animals are prone to thymic lymphomas (seen in ~20% of animals)

integument

increased skin papilloma incidence ( J:68981 )

• Background Sensitivity: animals are prone to skin papillomas (seen in ~25% of animals); tumors typically arising on ears and snout are predominantly pedunculated and show limited tendency to progress to squamous cell carcinoma

respiratory system

increased lung tumor incidence ( J:68981 )

• 100% of animals show multifocal tumors at time of death/sacrifice

• tumors are detectable at 1 week of age as small pleural nodules; multiplicity and size of tumors increases with age, and ultimately result in respiratory distress and death

• tumors range from mild hyperplasia/dysplasia to overt carcinoma; small lesions consist of hyperplastic alveolar epithelium

• in older mice, infrequent metastases to thoracic lymph nodes, the kidney and other visceral organs

increased lung adenoma incidence ( J:68981 )

• as lesions enlarge, they form small alveolar adenomas; some show areas of glandular differentiation

increased lung adenocarcinoma incidence ( J:68981 )

• 5-10% of tumors have features of well-differentiated human papillary adenocarcinoma

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:68981

Genotype
MGI:3814436

cx3

• Allelic Composition: Kras^tm2Tyj/Kras⁺; Trp53^tm1Glo/Trp53⁺
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd

mortality/aging

premature death ( J:129627 )

• average lifespan is 266 days with female mice exhibiting shorter lifespans than male mice

neoplasm

increased metastatic potential ( J:129627 )

• lung adenocarcinomas and mesothelioma are highly invasive and metastatic with metastatic lesions observed in the lymph nodes and liver

• 19 of 52 mice with lung adenocarcinomas exhibit metastasis compared to only 2 of 44 Kras^tm2Tyj heterozygotes

abnormal tumor morphology ( J:129627 )

• 81.8% of mice with end-stage lung adenocarcinomas exhibit loss of heterozygosity of the Trp53 wild-type allele

increased tumor incidence ( J:129627 )

• mice develop adenocarcinomas, adenomas, lymphomas, mesotheliomas, angiosarcomas, fibrosarcomas, pancreatic carcinomas, squamous carcinomas, and papillomas

increased lung adenoma incidence ( J:129627 )

• 52 of 56 mice develop atypical adenamatous hyperplasia, adenomas and adenocarcinomas

• most mice develop multiple large or diffuse adenocarcinomas that have glandular phenotypes or are poorly differentiated

increased lymphoma incidence ( J:129627 )

• some mice develop lung lymphomas

increased squamous cell carcinoma incidence ( J:129627 )

increased fibrosarcoma incidence ( J:129627 )

increased hemangiosarcoma incidence ( J:129627 )

increased mesothelioma incidence ( J:129627 )

• 13 of 56 mice develop mesothelioma 6 of which are peritoneal mesotheliomas

increased papilloma incidence ( J:129627 )

respiratory system

increased lung adenoma incidence ( J:129627 )

• 52 of 56 mice develop atypical adenamatous hyperplasia, adenomas and adenocarcinomas

• most mice develop multiple large or diffuse adenocarcinomas that have glandular phenotypes or are poorly differentiated

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:129627

Genotype
MGI:3770520

cx4

• Allelic Composition: Kras^tm2Tyj/Kras⁺; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:68981 )

neoplasm

increased tumor incidence ( J:68981 )

• double mutants display more malignant features than Kras heterozygous tumors, with marked cellular pleomorphism and anaplastic changes with giant cell formation

• mice have broader tumor spectrum compared to Kras or Trp53 heterozygotes, including histocytic sarcoma, medulloblastoma, osteosarcoma, and teratoma

increased T cell derived lymphoma incidence ( J:68981 )

increased skin papilloma incidence ( J:68981 )

increased fibrosarcoma incidence ( J:68981 )

increased hemangiosarcoma incidence ( J:68981 )

integument

increased skin papilloma incidence ( J:68981 )

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:68981 )

Genotype
MGI:3770615

cx5

• Allelic Composition: Dmtf1^tm1Cjs/Dmtf1⁺; Kras^tm2Tyj/Kras⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:126002 )

• mean survival time of double mutants is 41 weeks compared to 55 weeks for Kras^LA+/-, Dmtf1-sufficient mice

neoplasm

increased T cell derived lymphoma incidence ( J:126002 )

• ~30% of mice develop thymic lymphomas

increased skin papilloma incidence ( J:126002 )

• 20-30% of animals develop tail papillomas

increased cholangiocarcinoma incidence ( J:126002 )

• one case of cholangiocarcinoma was observed

abnormal metastatic potential ( J:126002 )

• <5% of animals show distant metastases (liver/intr-abdominal or leg) of lung tumors, while no metastases are observed in Kras^LA+/-, Dmtf1-sufficient mice

increased neurofibroma incidence ( J:126002 )

• one case of neurofibroma was observed

increased osteosarcoma incidence ( J:126002 )

• one case of osteosarcoma was observed

increased lung tumor incidence ( J:126002 )

• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion

increased lung adenoma incidence ( J:126002 )

• all mice develop lung adenomas or lung adenocarcinomas

increased lung adenocarcinoma incidence ( J:126002 )

• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in Kras^LA+/- single mutants

• number of tumor nodules increase as animals become sick, with trend to increased nodule size

decreased tumor latency ( J:126002 )

• tumorigenesis is accelerated relative to heterozygous Kras, wild-type Dmtf1 mice

integument

increased skin papilloma incidence ( J:126002 )

• 20-30% of animals develop tail papillomas

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:126002 )

• ~30% of mice develop thymic lymphomas

liver/biliary system

increased cholangiocarcinoma incidence ( J:126002 )

• one case of cholangiocarcinoma was observed

skeleton

increased osteosarcoma incidence ( J:126002 )

• one case of osteosarcoma was observed

nervous system

increased neurofibroma incidence ( J:126002 )

• one case of neurofibroma was observed

respiratory system

increased lung tumor incidence ( J:126002 )

• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion

increased lung adenoma incidence ( J:126002 )

• all mice develop lung adenomas or lung adenocarcinomas

increased lung adenocarcinoma incidence ( J:126002 )

• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in Kras^LA+/- single mutants

• number of tumor nodules increase as animals become sick, with trend to increased nodule size

Genotype
MGI:3770616

cx6

• Allelic Composition: Dmtf1^tm1Cjs/Dmtf1^tm1Cjs; Kras^tm2Tyj/Kras⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:126002 )

• mean survival time of double mutants is 36 weeks compared to 55 weeks for Kras^+/-, Dmtf1-sufficient mice

neoplasm

increased ovary tumor incidence ( J:126002 )

♀ • one case of ovarian cystic adenoma was observed

increased T cell derived lymphoma incidence ( J:126002 )

• ~20% of mice develop thymic lymphomas

increased skin papilloma incidence ( J:126002 )

• 30-40% of animals develop tail papillomas

abnormal metastatic potential ( J:126002 )

• <5% of animals show distant metastases (liver/intr-abdominal or leg) of lung tumors, while no metastases are observed in Kras^LA+/-, Dmtf1-sufficient mice

increased lung tumor incidence ( J:126002 )

• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion

increased lung adenoma incidence ( J:126002 )

• all mice develop lung adenomas or lung adenocarcinomas

increased lung adenocarcinoma incidence ( J:126002 )

• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in Kras^LA+/- single mutants

• number of tumor nodules increase as animals become sick, with trend to increased nodule size

decreased tumor latency ( J:126002 )

• tumorigenesis is accelerated relative to heterozygous Kras, wild-type Dmtf1 mice

integument

increased skin papilloma incidence ( J:126002 )

• 30-40% of animals develop tail papillomas

endocrine/exocrine glands

increased ovary tumor incidence ( J:126002 )

♀ • one case of ovarian cystic adenoma was observed

increased T cell derived lymphoma incidence ( J:126002 )

• ~20% of mice develop thymic lymphomas

reproductive system

increased ovary tumor incidence ( J:126002 )

♀ • one case of ovarian cystic adenoma was observed

respiratory system

increased lung tumor incidence ( J:126002 )

• ~50% of largest tumors are well, moderately, or poorly differentiated adenocarcinomas, with signs of intrabronchial or intravascular invasion

increased lung adenoma incidence ( J:126002 )

• all mice develop lung adenomas or lung adenocarcinomas

increased lung adenocarcinoma incidence ( J:126002 )

• greater than 50% of mice develop lung carcinomas by 40 weeks of age, and tumors are significantly larger than those found in Kras^LA+/- single mutants

• number of tumor nodules increase as animals become sick, with trend to increased nodule size

Genotype
MGI:3770519

cx7

• Allelic Composition: Kras^tm2Tyj/Kras⁺; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:68981 )

• mice have reduced life spans compared to Kras or Trp53 heterozygous mice, or Trp53 homozygotes

neoplasm

increased tumor incidence ( J:68981 )

• double mutants display more malignant features than Kras heterozygous tumors, with marked cellular pleomorphism and anaplastic changes with giant cell formation

• mice have broader tumor spectrum compared to Kras or Trp53 heterozygotes, including histocytic sarcoma, medulloblastoma, osteosarcoma, and teratoma

increased T cell derived lymphoma incidence ( J:68981 )

• Background Sensitivity: about 40% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background

increased skin papilloma incidence ( J:68981 )

• about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background

increased fibrosarcoma incidence ( J:68981 )

• about 30% of double mutants develop fibrosarcoma

increased hemangiosarcoma incidence ( J:68981 )

• about 30% of double mutants develop hemangiosarcoma

integument

increased skin papilloma incidence ( J:68981 )

• about 40% of mice develop skin papillomas, with slightly higher incidence than on mixed 129 and C57BL/6 background

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:68981 )

• Background Sensitivity: about 40% of animals develop thymic lymphoma; incidence is higher than on pure 129/Sv background