Phenotypes associated with this allele

• Allele Symbol: Tg(tetO-Kras2)12Hev
• Allele Name: transgene insertion 12, Harold E Varmus
• Allele ID: MGI:2179992
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor^+ Ptf1a^tm1.1(cre)Cvw/Ptf1a^+ Tg(tetO-Kras2)12Hev/0 Trp53^tm1Tyj/Trp53^+	involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6J * FVB/N	MGI:5569005
cn2	Gt(ROSA)26Sor^tm1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor^+ Ptf1a^tm1.1(cre)Cvw/Ptf1a^+ Tg(tetO-Kras2)12Hev/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:5569002
cx3	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Kras2)12Hev/0	involves: 129 * C57BL/6 * FVB/N	MGI:5912341
cx4	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Kras2)12Hev/0	involves: 129 * C57BL/6J * FVB/N * SJL	MGI:5912294
cx5	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Kras2)12Hev/0 Trp53^tm1Tyj/Trp53^+	involves: 129S2/SvPas * C57BL/6 * FVB/N	MGI:5912344
cx6	Tg(MMTV-Myc)141-3Led/0 Tg(MMTV-rtTA)1Lach/0 Tg(tetO-Kras2)12Hev/0	involves: C57BL/6J * CD-1 * FVB/N	MGI:5827760
cx7	Tg(MMTV-rtTA)1Lach/0 Tg(tetO-Kras2)12Hev/0 Tg(tetO-MYC)1Lach/0	involves: FVB/N	MGI:5827758
cx8	Tg(MMTV-rtTA)1Lach/0 Tg(tetO-Kras2)12Hev/0	involves: FVB/N	MGI:5827756
tg9	Tg(tetO-Kras2)12Hev/0	involves: FVB/N	MGI:5912342

Genotype
MGI:5569005

cn1

• Allelic Composition: Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺; Ptf1a^{tm1.1(cre)Cvw}/Ptf1a⁺; Tg(tetO-Kras2)12Hev/0; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129X1/SvJ * C57BL/6J * FVB/N

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

mortality/aging

premature death ( J:184378 )

• mice die between 8 and 18 weeks after doxycycline (dox) treatment to induce Kras2 expression due to pancreatic ductal adenocarinoma

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:184378 )

• mice develop invasive adenocarcinoma between 8 and 18 weeks after dox treatment, with some cases showing hemorrhagic ascites, with admixed poorly differentiated and well-differentiated areas and duodenal invasion

• mice in which dox is removed recover their health and show pancreatic tumor regression resulting in a small pancreatic remnant

increased pancreatic intraepithelial neoplasia incidence ( J:184378 )

• adult mice treated with dox 72 hours prior to injection with cholecystokinin analog cerulein to induce acute pancreatitis develop PanINs, dilated ducts with the presence of intracellular mucins, and extensive fibroinflammatory stroma

homeostasis/metabolism

increased susceptibility to injury ( J:184378 )

• adult mice treated with dox for 5 weeks prior to injection with cholecystokinin analog cerulein to induce acute pancreatitis exhibit a small, translucent remnant of pancreatic tissue, without fibrosis or PanIN lesions

• when dox is removed after pancreatitis induction, mice show show normal acini interspersed with dilated ducts and acinar-ductal metaplasia, fibrosis and occasional lipomatosis, but with minimal inflammatory infiltrate, and reduced proliferation

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:184378 )

• mice develop invasive adenocarcinoma between 8 and 18 weeks after dox treatment, with some cases showing hemorrhagic ascites, with admixed poorly differentiated and well-differentiated areas and duodenal invasion

• mice in which dox is removed recover their health and show pancreatic tumor regression resulting in a small pancreatic remnant

increased pancreatic intraepithelial neoplasia incidence ( J:184378 )

• adult mice treated with dox 72 hours prior to injection with cholecystokinin analog cerulein to induce acute pancreatitis develop PanINs, dilated ducts with the presence of intracellular mucins, and extensive fibroinflammatory stroma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:184378

Genotype
MGI:5569002

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺; Ptf1a^{tm1.1(cre)Cvw}/Ptf1a⁺; Tg(tetO-Kras2)12Hev/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

neoplasm

increased pancreas tumor incidence ( J:184378 )

• 1 of 2 mice treated with doxycycline (dox) at 4-6 weeks of age show frank adenocarcinoma by 23 weeks on dox

• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein to induce acute pancreatitis show low- and high-grade PanIN lesions interspersed with areas of carcinoma in situ at 5 weeks after induction

increased pancreatic intraepithelial neoplasia incidence ( J:184378 )

• mice treated with doxycycline (dox) at 4-6 weeks of age to induce Kras2 expression begin to show low-grade pancreatic intraepithelial neoplasia (PanIN) beginning at 3 weeks after dox treatment

• mice treated with dox at 4-6 weeks of age show PanIN, surrounded by areas of fibrosis and embedded in the acinar parenchyma after 18 weeks on dox and by 23 weeks, large areas of the pancreatic parenchyma are substituted with PanIN lesions of different grade, with frank adenocarcinoma seen in 1 of 2 mice

• mice kept on dox for 23 weeks show reversion of PanINs when dox is removed for 2 weeks

• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein, to induce acute pancreatitis, develop low- and high-grade PanIN lesions at 5 weeks after induction

• mice treated with dox 72 hours prior to induction of pancreatitis also show reversion of PanINs when dox is removed for 2 weeks

homeostasis/metabolism

increased susceptibility to injury ( J:184378 )

• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein to induce acute pancreatitis show impaired recovery from pancreatitis, showing acinar-ductal metaplasia with progressive accumulation of fibrotic stroma at 1 week after induction, replacement of the whole pancreatic parenchyma with ductal structures and signs of PanINs at 3 weeks after induction, and low- and high-grade PanIN lesions interspersed with areas of carcinoma in situ at 5 weeks after induction compared to adult mice without dox which show completely resolved damage

• mice kept on dox for 5 weeks prior to induction of pancreatitis and then dox removal for 2 weeks show incomplete repair process resulting in a small, fibrotic pancreas with fewer acini; after 5 weeks of dox removal, no PanINs are observed however, the pancreas appears fibrotic and is small

endocrine/exocrine glands

small pancreas ( J:184378 )

• mice kept on dox for 5 weeks following pancreatitis induction show an increase in apoptotic cells and small pancreas size upon removal of dox

pancreatic acinar-to-ductal metaplasia ( J:184378 )

• mice treated with dox at 4-6 weeks of age begin to show acinar-ductal metaplasia beginning at 3 weeks after dox treatment

increased pancreas tumor incidence ( J:184378 )

• 1 of 2 mice treated with doxycycline (dox) at 4-6 weeks of age show frank adenocarcinoma by 23 weeks on dox

• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein to induce acute pancreatitis show low- and high-grade PanIN lesions interspersed with areas of carcinoma in situ at 5 weeks after induction

increased pancreatic intraepithelial neoplasia incidence ( J:184378 )

• mice treated with doxycycline (dox) at 4-6 weeks of age to induce Kras2 expression begin to show low-grade pancreatic intraepithelial neoplasia (PanIN) beginning at 3 weeks after dox treatment

• mice treated with dox at 4-6 weeks of age show PanIN, surrounded by areas of fibrosis and embedded in the acinar parenchyma after 18 weeks on dox and by 23 weeks, large areas of the pancreatic parenchyma are substituted with PanIN lesions of different grade, with frank adenocarcinoma seen in 1 of 2 mice

• mice kept on dox for 23 weeks show reversion of PanINs when dox is removed for 2 weeks

• adult mice treated with dox 72 hours prior to injection with the cholecystokinin analog cerulein, to induce acute pancreatitis, develop low- and high-grade PanIN lesions at 5 weeks after induction

• mice treated with dox 72 hours prior to induction of pancreatitis also show reversion of PanINs when dox is removed for 2 weeks

Genotype
MGI:5912341

cx3

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-Kras2)12Hev/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

neoplasm

increased lung tumor incidence ( J:73468 )

• in doxycycline-treated mice

• however, tumors regress after doxycycline withdrawal due to apoptosis

increased lung adenoma incidence ( J:73468 )

• multiple large, solid-type adenomas in doxycycline-treated mice

increased lung adenocarcinoma incidence ( J:73468 )

• in doxycycline-treated mice

respiratory system

increased lung tumor incidence ( J:73468 )

• in doxycycline-treated mice

• however, tumors regress after doxycycline withdrawal due to apoptosis

increased lung adenoma incidence ( J:73468 )

• multiple large, solid-type adenomas in doxycycline-treated mice

increased lung adenocarcinoma incidence ( J:73468 )

• in doxycycline-treated mice

abnormal respiratory system physiology ( J:73468 )

• proliferative alveolar lesions and focal hyperplasia of type II pneumocytes in doxycycline-treated mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lung adenocarcinoma		DOID:3910		J:73468

Genotype
MGI:5912294

cx4

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-Kras2)12Hev/0
• Genetic Background: involves: 129 * C57BL/6J * FVB/N * SJL

neoplasm

increased lung tumor incidence ( J:73468 )

• doxycycline-treated mice initiate lung tumors more rapidly than in Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice with a more malignant phenotype

• however, tumors regress after doxycycline withdrawal due to apoptosis

increased lung adenocarcinoma incidence ( J:73468 , J:166963 )

• more sooner in doxycycline-treated mice compared with Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice (J:73468)

• in doxycycline-treated mice (J:166963)

respiratory system

increased lung tumor incidence ( J:73468 )

• doxycycline-treated mice initiate lung tumors more rapidly than in Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice with a more malignant phenotype

• however, tumors regress after doxycycline withdrawal due to apoptosis

increased lung adenocarcinoma incidence ( J:73468 , J:166963 )

• more sooner in doxycycline-treated mice compared with Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice (J:73468)

• in doxycycline-treated mice (J:166963)

Genotype
MGI:5912344

cx5

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-Kras2)12Hev/0; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * FVB/N

neoplasm

increased lung tumor incidence ( J:73468 )

• doxycycline-treated mice initiate lung tumors more rapidly than in Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice with a more malignant phenotype

increased lung adenocarcinoma incidence ( J:73468 )

• more sooner in doxycycline-treated mice compared with Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice

respiratory system

increased lung tumor incidence ( J:73468 )

• doxycycline-treated mice initiate lung tumors more rapidly than in Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice with a more malignant phenotype

increased lung adenocarcinoma incidence ( J:73468 )

• more sooner in doxycycline-treated mice compared with Tg(Scgb1a1-rtTA)1Jaw Tg(tetO-Kras2)12Hev mice

Genotype
MGI:5827760

cx6

• Allelic Composition: Tg(MMTV-Myc)141-3Led/0; Tg(MMTV-rtTA)1Lach/0; Tg(tetO-Kras2)12Hev/0
• Genetic Background: involves: C57BL/6J * CD-1 * FVB/N

neoplasm

increased mammary gland tumor incidence ( J:133578 )

♀ • mice fed doxycycline develop tumors in all mammary glands within 10 weeks of induction, with a median latency between 6 and 8 weeks

♀ • removal of doxycycline results in apoptosis and reduced proliferation of tumors after doxycycline withdrawal, almost all of the transformed mammary glands completely regress to a nonpalpable state, however, hyperplastic changes persist in the glands

♀ • after doxycycline withdrawal, almost all of the transformed mammary glands completely regress to a nonpalpable state, however, hyperplastic changes persist in the glands

♀ • mammary tumors develop after withdrawal of doxycycline at a median age of 33 weeks, indicating recurrent tumors

♀ • tumor recurrence is associated with reactivation of oncogenic transgenes and somatic mutations in the rtTA transgene

integument

increased mammary gland tumor incidence ( J:133578 )

♀ • mice fed doxycycline develop tumors in all mammary glands within 10 weeks of induction, with a median latency between 6 and 8 weeks

♀ • removal of doxycycline results in apoptosis and reduced proliferation of tumors after doxycycline withdrawal, almost all of the transformed mammary glands completely regress to a nonpalpable state, however, hyperplastic changes persist in the glands

♀ • after doxycycline withdrawal, almost all of the transformed mammary glands completely regress to a nonpalpable state, however, hyperplastic changes persist in the glands

♀ • mammary tumors develop after withdrawal of doxycycline at a median age of 33 weeks, indicating recurrent tumors

♀ • tumor recurrence is associated with reactivation of oncogenic transgenes and somatic mutations in the rtTA transgene

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:133578 )

♀ • mice fed doxycycline develop tumors in all mammary glands within 10 weeks of induction, with a median latency between 6 and 8 weeks

♀ • removal of doxycycline results in apoptosis and reduced proliferation of tumors after doxycycline withdrawal, almost all of the transformed mammary glands completely regress to a nonpalpable state, however, hyperplastic changes persist in the glands

♀ • after doxycycline withdrawal, almost all of the transformed mammary glands completely regress to a nonpalpable state, however, hyperplastic changes persist in the glands

♀ • mammary tumors develop after withdrawal of doxycycline at a median age of 33 weeks, indicating recurrent tumors

♀ • tumor recurrence is associated with reactivation of oncogenic transgenes and somatic mutations in the rtTA transgene

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:133578

Genotype
MGI:5827758

cx7

• Allelic Composition: Tg(MMTV-rtTA)1Lach/0; Tg(tetO-Kras2)12Hev/0; Tg(tetO-MYC)1Lach/0
• Genetic Background: involves: FVB/N

neoplasm

increased mammary gland tumor incidence ( J:133578 )

♀ • diffuse mammary hyperplasia is seen at 7 days after doxycycline administration, numerous tumor nodules are seen throughout the glandular tree at 14 days and confluent tumors are present at 21 days

♀ • removal of doxycycline results in apoptosis and reduced proliferation of tumors

♀ • after doxycycline withdrawal, almost all of the transformed mammary glands completely regress to a nonpalpable state within 2 weeks

♀ • solitary mammary tumors develop after withdrawal of doxycycline in 20 of 36 mice at a median age of 53 weeks, indicating recurrent tumors

♀ • in the absence of doxycycline, only one of 31 mice develop a mammary tumor

♀ • tumor recurrence is associated with reactivation of oncogenic transgenes and somatic mutations in the rtTA transgene

integument

increased mammary gland tumor incidence ( J:133578 )

♀ • diffuse mammary hyperplasia is seen at 7 days after doxycycline administration, numerous tumor nodules are seen throughout the glandular tree at 14 days and confluent tumors are present at 21 days

♀ • removal of doxycycline results in apoptosis and reduced proliferation of tumors

♀ • after doxycycline withdrawal, almost all of the transformed mammary glands completely regress to a nonpalpable state within 2 weeks

♀ • solitary mammary tumors develop after withdrawal of doxycycline in 20 of 36 mice at a median age of 53 weeks, indicating recurrent tumors

♀ • in the absence of doxycycline, only one of 31 mice develop a mammary tumor

♀ • tumor recurrence is associated with reactivation of oncogenic transgenes and somatic mutations in the rtTA transgene

mammary gland hyperplasia ( J:133578 )

♀ • diffuse mammary hyperplasia is seen at 7 days after doxycycline administration

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:133578 )

♀ • diffuse mammary hyperplasia is seen at 7 days after doxycycline administration, numerous tumor nodules are seen throughout the glandular tree at 14 days and confluent tumors are present at 21 days

♀ • removal of doxycycline results in apoptosis and reduced proliferation of tumors

♀ • after doxycycline withdrawal, almost all of the transformed mammary glands completely regress to a nonpalpable state within 2 weeks

♀ • solitary mammary tumors develop after withdrawal of doxycycline in 20 of 36 mice at a median age of 53 weeks, indicating recurrent tumors

♀ • in the absence of doxycycline, only one of 31 mice develop a mammary tumor

♀ • tumor recurrence is associated with reactivation of oncogenic transgenes and somatic mutations in the rtTA transgene

mammary gland hyperplasia ( J:133578 )

♀ • diffuse mammary hyperplasia is seen at 7 days after doxycycline administration

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:114480

Genotype
MGI:5827756

cx8

• Allelic Composition: Tg(MMTV-rtTA)1Lach/0; Tg(tetO-Kras2)12Hev/0
• Genetic Background: involves: FVB/N

neoplasm

increased mammary gland tumor incidence ( J:133578 )

♀ • mice fed doxycycline after weaning develop mammary gland hyperplasia, progress to hyperplastic alveolar nodules, and then palpable oligofocal mammary tumors with a median latency of 22 weeks

integument

increased mammary gland tumor incidence ( J:133578 )

♀ • mice fed doxycycline after weaning develop mammary gland hyperplasia, progress to hyperplastic alveolar nodules, and then palpable oligofocal mammary tumors with a median latency of 22 weeks

mammary gland hyperplasia ( J:133578 )

♀ • mice fed doxycycline after weaning develop mammary gland hyperplasia as early as one week after induction

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:133578 )

♀ • mice fed doxycycline after weaning develop mammary gland hyperplasia, progress to hyperplastic alveolar nodules, and then palpable oligofocal mammary tumors with a median latency of 22 weeks

mammary gland hyperplasia ( J:133578 )

♀ • mice fed doxycycline after weaning develop mammary gland hyperplasia as early as one week after induction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:133578

Genotype
MGI:5912342

tg9

• Allelic Composition: Tg(tetO-Kras2)12Hev/0
• Genetic Background: involves: FVB/N

neoplasm

neoplasm ( J:73468 )

N • doxycycline-treated mice doe not develop lung lesions