Phenotypes associated with this allele

• Allele Symbol: Tg(Cebpb-tTA)5Bjd
• Allele Name: transgene insertion 5, Hermann Bujard
• Allele ID: MGI:3056818
• Summary: 11 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Rb1^tm3Tyj/Rb1^tm3Tyj Tg(tetO-MYC)36aBop/0 Tg(Cebpb-tTA)5Bjd/0	involves: FVB/N * NMRI	MGI:5008419
cx2	Tg(Cebpb-tTA)5Bjd/0 Tg(tetO-MYC,-OVAL)#Gtgm/0	B6J.Cg-Tg(Cebpb-tTA)5Bjd Tg(tetO-MYC,-OVAL)#Gtgm	MGI:6197223
cx3	Dbt^tm1Geh/Dbt^tm1Geh Tg(tetO-DBT)525AGeh/0 Tg(Cebpb-tTA)5Bjd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB * NMRI	MGI:3704920
cx4	Dbt^tm1Geh/Dbt^tm1Geh Tg(tetO-DBT)A1Geh/0 Tg(Cebpb-tTA)5Bjd/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB * NMRI	MGI:3704913
cx5	Kdr^tm1Jrt/Kdr^+ Tg(tetO-Kdr*)4377.5Rwng/0 Tg(Cebpb-tTA)5Bjd/0	involves: 129S1/Sv * 129X1/SvJ * FVB/N * NMRI	MGI:3810713
cx6	Col1a1^tm3(tetO-Fosl1,-DsRed)Wag/Col1a1^+ Tg(Cebpb-tTA)5Bjd/0	involves: 129S4/SvJae * C57BL/6 * NMRI	MGI:5586503
cx7	Col1a1^tm2(tetO-Fosl2,-DsRed)Wag/Col1a1^+ Tg(Cebpb-tTA)5Bjd/0	involves: 129S4/SvJae * C57BL/6 * NMRI	MGI:5586504
cx8	Col1a1^tm4(tetO-Jun/Fosl2)Wag/Col1a1^+ Tg(Cebpb-tTA)5Bjd/0	involves: 129S4/SvJae * C57BL/6 * NMRI	MGI:5586552
cx9	Tg(tetO-MET)23Rwng/0 Tg(Cebpb-tTA)5Bjd/0	involves: FVB/N * NMRI	MGI:3810811
cx10	Tg(tetO-Kdr*)4377.5Rwng/0 Tg(Cebpb-tTA)5Bjd/0	involves: FVB/N * NMRI	MGI:3810712
cx11	Tg(tetO-MYC)36aBop/0 Tg(Cebpb-tTA)5Bjd/0	involves: FVB/N * NMRI	MGI:4358091

Genotype
MGI:5008419

cn1

• Allelic Composition: Rb1^tm3Tyj/Rb1^tm3Tyj; Tg(tetO-MYC)36aBop/0; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: FVB/N * NMRI

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

Increase in ploidy in hepatocytes of tamoxifen-treated Rb1^tm3Tyj/Rb1^tm3Tyj Tg(tetO-MYC)36aBop/0 Tg(Cebpb-tTA)5Bjd/0 mice

mortality/aging

decreased tumor-free survival time ( J:172430 )

• median survival of mutants is 27 weeks following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase

• median survival of mutants with tumors is 16.5 weeks following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase

liver/biliary system

increased liver tumor incidence ( J:172430 )

• following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase, some mice develop liver tumors composed of multiple fleshy vascular nodules

increased hepatocellular carcinoma incidence ( J:172430 )

• tumors of mice injected with adenovirus expressing Cre recombinase and without doxycycline to induce MYC expression are composed of hepatocellular neoplasms characterized by sheets of cells with occasional mitotic figure, slightly pleomorphic nuclei, and prominent nucleoli

• tumors show a range of differentiation between well- and moderately-differentiated hepatocellular carcinoma

cellular

polyploidy ( J:172430 )

• following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase, adult liver cells exhibit an increase in polyploidy

neoplasm

increased liver tumor incidence ( J:172430 )

• following withdrawal of doxycycline and intrasplenic injection of adenovirus expressing Cre recombinase, some mice develop liver tumors composed of multiple fleshy vascular nodules

increased hepatocellular carcinoma incidence ( J:172430 )

• tumors of mice injected with adenovirus expressing Cre recombinase and without doxycycline to induce MYC expression are composed of hepatocellular neoplasms characterized by sheets of cells with occasional mitotic figure, slightly pleomorphic nuclei, and prominent nucleoli

• tumors show a range of differentiation between well- and moderately-differentiated hepatocellular carcinoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:172430

Genotype
MGI:6197223

cx2

• Allelic Composition: Tg(Cebpb-tTA)5Bjd/0; Tg(tetO-MYC,-OVAL)#Gtgm/0
• Genetic Background: B6J.Cg-Tg(Cebpb-tTA)5Bjd Tg(tetO-MYC,-OVAL)#Gtgm

mortality/aging

premature death ( J:186226 )

• mice become moribund with multifocal hepatocellular carcinoma within 5-8 weeks when doxycycline is removed at birth

neoplasm

increased hepatocellular carcinoma incidence ( J:186226 )

• mice develop multifocal hepatocellular carcinoma within 5-8 weeks of birth, with initial tumor foci as early as 4 weeks after induction with the removal of doxycline

immune system

abnormal immune tolerance ( J:186226 )

• CD8+ T cells from Tg(TcraTcrb)1100Mjb expressing mice transferred into these mice are hyporesponsive and fail to become cytotoxic effect cells indicating cytotoxic T lymphocyte tolerance induction

liver/biliary system

increased hepatocellular carcinoma incidence ( J:186226 )

• mice develop multifocal hepatocellular carcinoma within 5-8 weeks of birth, with initial tumor foci as early as 4 weeks after induction with the removal of doxycline

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:186226

Genotype
MGI:3704920

cx3

• Allelic Composition: Dbt^tm1Geh/Dbt^tm1Geh; Tg(tetO-DBT)525AGeh/0; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB * NMRI

mortality/aging

premature death ( J:119973 )

• only 12% (2/16) transgenic mice survive to 20 weeks; two surviving mice live to 40 and 60 weeks, respectively

postnatal lethality ( J:119973 )

• approximately 11% of pups surviving to weaning have this genotype, compared to a theoretical survival rate or 14%, indicating high degree of rescue of the Dbt-deficient phenotype

homeostasis/metabolism

abnormal circulating amino acid level ( J:119973 )

• blood levels of glutamate are reduced compared to controls, but greater than in Dbt^tm1Geh homozygotes

• BCAA/alanine (BCAA -branched-chain amino acids - leucine + isoleucine + valine) values are intermediate between controls and Dbt^tm1Geh homozygotes between 4-10 weeks of age

abnormal enzyme/coenzyme activity ( J:119973 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maple syrup urine disease		DOID:9269	OMIM:246900 OMIM:248600 OMIM:615135	J:119973

Genotype
MGI:3704913

cx4

• Allelic Composition: Dbt^tm1Geh/Dbt^tm1Geh; Tg(tetO-DBT)A1Geh/0; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB * NMRI

mortality/aging

premature death ( J:119973 )

• transgenic mice survival is only ~16 weeks, when mice become moribund and are sacrificed

postnatal lethality ( J:119973 )

• approximately 4% of pups surviving to weaning have this genotype, compared to a theoretical survival rate or 14%, indicating partial rescue of the Dbt^tm1Geh phenotype

homeostasis/metabolism

abnormal circulating amino acid level ( J:119973 )

• blood levels of alanine, glutamate, and glutamine are reduced compared to controls, but greater than in Dbt^tm1Geh homozygous mice

• BCAA/alanine (BCAA -branched-chain amino acids - leucine + isoleucine + valine) values are intermediate between controls and Dbt-null mice between 4-7 weeks of age

abnormal enzyme/coenzyme activity ( J:119973 )

• levels of branched-chain keto acid dehydrogenase (BCKDH) activity are only 5-6% of controls levels, despite nearly equal protein levels, indicating suboptimal BCKDH activity of protein assembled with human E2

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maple syrup urine disease		DOID:9269	OMIM:246900 OMIM:248600 OMIM:615135	J:119973

Genotype
MGI:3810713

cx5

• Allelic Composition: Kdr^tm1Jrt/Kdr⁺; Tg(tetO-Kdr*)4377.5Rwng/0; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N * NMRI

liver/biliary system

abnormal liver development ( J:100427 )

• at E12.5, liver vasculature is less organized and vessels are dilated

• at E13.5, microvascular network is more disorganized with fewer branches than in control livers; newborns have very little microvascular network is observed

Genotype
MGI:5586503

cx6

• Allelic Composition: Col1a1^{tm3(tetO-Fosl1,-DsRed)Wag}/Col1a1⁺; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * NMRI

growth/size/body

increased liver weight ( J:213764 )

• in mice exposed to DCC

mortality/aging

mortality/aging ( J:213764 )

N • mice are viable

homeostasis/metabolism

decreased circulating cholesterol level ( J:213764 )

• in mice exposed to DCC

increased circulating cholesterol level ( J:210545 )

• mild in mice fed a high fat diet

increased circulating triglyceride level ( J:210545 )

• mild in mice fed a high fat diet

decreased circulating interleukin-6 level ( J:210545 )

decreased circulating alanine transaminase level ( J:210545 , J:213764 )

• compared with control mice when fed a high fat diet (J:210545)

• reversion of high fat diet-induced elevations in alanine transaminase level following withdrawal of doxycycline (J:210545)

• in mice exposed to DCC (J:213764)

impaired glucose tolerance ( J:210545 )

• slightly worse than in control mice fed a high fat diet

insulin resistance ( J:210545 )

• slightly worse than in control mice when fed a high fat diet

increased bile salt level ( J:213764 )

• relative to body weight in mice exposed to DCC compared with control mice

decreased liver triglyceride level ( J:210545 )

• compared with control mice when fed a high fat diet

• reversion of high fat diet-induced steatosis following withdrawal of doxycycline

• however, adenorival Pparg restores diet-induced steatosis

decreased susceptibility to injury ( J:213764 )

• mice exposed to DCC exhibit reduced liver damage (increased relative liver weight and reduced ALT levels) compared with control mice

• mice subjected to acetaminophen-induced hepatotoxicity exhibit reduced liver damage compared with control mice

liver/biliary system

liver/biliary system phenotype ( J:213764 )

N • mice exhibit no signs of liver fibrosis and serum parameters

liver inflammation ( J:210545 )

• reduced compared with control mice fed a high fat diet

abnormal liver morphology ( J:210545 )

• less pale livers with a reduction in lipid droplets than in control mice when a high fat diet

increased liver weight ( J:213764 )

• in mice exposed to DCC

decreased liver triglyceride level ( J:210545 )

• compared with control mice when fed a high fat diet

• reversion of high fat diet-induced steatosis following withdrawal of doxycycline

• however, adenorival Pparg restores diet-induced steatosis

decreased liver weight ( J:210545 )

• compared with control mice when fed a high fat diet

• in mice fed a high fat diet following withdrawal of doxycycline

decreased susceptibility to diet-induced hepatic steatosis ( J:210545 )

• reduction in lipid droplets compared with control mice when fed a high fat diet

• reversion of high fat diet-induced steatosis following doxycycline treatment

• however, adenorival Pparg restores diet-induced steatosis

immune system

decreased circulating interleukin-6 level ( J:210545 )

liver inflammation ( J:210545 )

• reduced compared with control mice fed a high fat diet

Genotype
MGI:5586504

cx7

• Allelic Composition: Col1a1^{tm2(tetO-Fosl2,-DsRed)Wag}/Col1a1⁺; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * NMRI

liver/biliary system

decreased liver triglyceride level ( J:210545 )

• compared with control mice when fed a high fat diet

decreased susceptibility to diet-induced hepatic steatosis ( J:210545 )

• mice fed a high fat diet do not develop steatohepatitis unlike control mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:213764 )

N • mice subjected to acetaminophen-induced hepatotoxicity exhibit a normal response

decreased liver triglyceride level ( J:210545 )

• compared with control mice when fed a high fat diet

Genotype
MGI:5586552

cx8

• Allelic Composition: Col1a1^{tm4(tetO-Jun/Fosl2)Wag}/Col1a1⁺; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * NMRI

liver/biliary system

decreased liver triglyceride level ( J:210545 )

• compared with control mice when fed a high fat diet

decreased susceptibility to diet-induced hepatic steatosis ( J:210545 )

• mice fed a high fat diet do not develop steatohepatitis unlike control mice

homeostasis/metabolism

decreased liver triglyceride level ( J:210545 )

• compared with control mice when fed a high fat diet

Genotype
MGI:3810811

cx9

• Allelic Composition: Tg(tetO-MET)23Rwng/0; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: FVB/N * NMRI

mortality/aging

premature death ( J:69731 )

• mice from 2 lines (1 and 2) of double transgenic founders die within 2 months postpartum; early mortality can be prevented by repression of MET expression with doxycycline administration to mating parents, and then to pups until 4 weeks of age

• with this doxycycline treatment, animals appear normal until 10 months of age, then mice start dying

• mice from 2 other lines (3 and 4) of double transgenic parents are healthy at birth, then begin to die at 4 months of age

growth/size/body

cachexia ( J:69731 )

• animals dying without evidence of tumors are usually cachexic

enlarged liver ( J:69731 )

• pups are born with enlarged and fatty livers

liver/biliary system

enlarged liver ( J:69731 )

• pups are born with enlarged and fatty livers

abnormal hepatocyte morphology ( J:69731 )

• hepatocytes in foci of hyperplasia develop foamy cytoplasm containing fat deposits

• with progression of hyperplastic foci toward malignancy, cytologic changes are observed such as cellular and nuclear enlargement with disorganization of cell plate and lobular structures; malignant foci enlarge and develop trabeculae lined with endothelial cells, often separated from each other by blood-filled spaces

focal hepatic necrosis ( J:69731 )

• fully developed tumors often display areas of necrosis

hepatic steatosis ( J:69731 )

• pups are born with enlarged and fatty livers

increased hepatocellular carcinoma incidence ( J:69731 )

• 85% of animals dying after 10 months after receiving DOX till 4 weeks of age show hepatocellular carcinoma (HCC); incidence by 1 year is >60% in lines 1 and 2

• for lines 3 and 4, 85% of deaths are accompanied by HCC, which appears as an abdominal mass at 6 months of age or later; incidence by 1 year is 60%

• by 60 weeks of age, many small foci of hyperplasia are detected, often around central hepatic lobule and become more numerous, larger, and uniformly distributed by 4 months of age

• zones of progression to malignancy are observed within hyperplasias by 6 months, with cells in the zones showing poor organization and less differentiation than normal livers

• majority of moribund mice treated with doxycycline regain health tumors nearly regress completely, with liver morphology becoming almost normal by 4 months of treatment

• fully developed tumors often display areas of necrosis

jaundice ( J:69731 )

• animals dying without evidence of tumors display jaundice

neoplasm

increased hepatocellular carcinoma incidence ( J:69731 )

• 85% of animals dying after 10 months after receiving DOX till 4 weeks of age show hepatocellular carcinoma (HCC); incidence by 1 year is >60% in lines 1 and 2

• for lines 3 and 4, 85% of deaths are accompanied by HCC, which appears as an abdominal mass at 6 months of age or later; incidence by 1 year is 60%

• by 60 weeks of age, many small foci of hyperplasia are detected, often around central hepatic lobule and become more numerous, larger, and uniformly distributed by 4 months of age

• zones of progression to malignancy are observed within hyperplasias by 6 months, with cells in the zones showing poor organization and less differentiation than normal livers

• majority of moribund mice treated with doxycycline regain health tumors nearly regress completely, with liver morphology becoming almost normal by 4 months of treatment

• fully developed tumors often display areas of necrosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hepatocellular carcinoma		DOID:684	OMIM:114550	J:69731

Genotype
MGI:3810712

cx10

• Allelic Composition: Tg(tetO-Kdr*)4377.5Rwng/0; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: FVB/N * NMRI

mortality/aging

perinatal lethality, incomplete penetrance ( J:100427 )

• between 25% and 38% of pups are stillborn

liver/biliary system

liver/biliary system phenotype ( J:100427 )

N • liver glycogen and albumin levels are comparable to control animals

abnormal liver morphology ( J:100427 )

• livers from neonates display a decrease in blood vessels

• livers of all newborn animals are dark red in appearance in contrast to pink color of control livers

• fewer endothelial cells (ECs) are present in mutant liver vasculature; ECs are present but are less organized and more discontinuous than in controls

• fewer or collapsed-appearing sinusoidal channels are observed

• livers have a sparse and poorly developed sinusoidal network with numerous blood cells in the disrupted sinusoidal spaces

• parenchymal cells contain very few or no lipid droplets

• morphology of space of Disse is abnormal, showing large gaps between sinusoidal epithelial cells (SECs) and hepatocytes

• sinusoidal epithelium lacks fenestrations seen in normal livers

abnormal hepatocyte morphology ( J:100427 )

• hepatocytes are more scattered than in control livers and many are oddly shaped with fewer microvilli projections into the space of Disse

abnormal liver physiology ( J:100427 )

• there is increase in red blood cells in liver due to defective circulation

• livers show a significant defect in lipoprotein uptake compared to controls

jaundice ( J:100427 )

• 30 to 63% of newborns are jaundiced; suppression of transgenic Kdr by doxycycline treatement of dams during embryogenesis eliminates jaundice that is observed in untreated animals

cardiovascular system

abnormal blood vessel morphology ( J:100427 )

• decreased number of blood vessels in liver

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:100427 )

N • serum bilirubin levels are normal

Genotype
MGI:4358091

cx11

• Allelic Composition: Tg(tetO-MYC)36aBop/0; Tg(Cebpb-tTA)5Bjd/0
• Genetic Background: involves: FVB/N * NMRI

mortality/aging

premature death ( J:93899 )

• following withdrawal of doxycycline, all mice succumb to liver tumors within 2 weeks

decreased tumor-free survival time ( J:172430 )

• median survival of mutants is 31 weeks following doxycycline withdrawal to induce MYC expression

• median survival of mutants with tumors is 27 weeks following doxycycline withdrawal to induce MYC expression

neoplasm

increased liver tumor incidence ( J:93899 , J:172430 )

• following withdrawal of doxycycline, mice develop tumors with a latency of 12 weeks and all mice succumb to liver tumors within 2 weeks (J:93899)

• liver tumors that develop in mice after doxycycline withdrawal are invasive and metastasis into the thoracic cavity and lung parenchyma (J:93899)

• however, re-establishment of doxycycline-treatment produces rapid and sustained tumor regression (J:93899)

• repeated withdrawal and treatment with doxycyclineinduces and represses, respectively, tumor formation (J:93899)

increased hepatoblastoma incidence ( J:93899 )

• liver tumors that develop in mice after doxycycline withdrawal resemble hepatocellular carcinomas and/or hepatoblastomas

increased hepatocellular carcinoma incidence ( J:93899 , J:172430 , J:186226 , J:190067 )

• liver tumors that develop in mice after doxycycline withdrawal resemble hepatocellular carcinomas and/or hepatoblastomas (J:93899)

• tumors that form in mice after doxycycline withdrawal are composed of hepatocellular neoplasms characterized by sheets of cells with occasional mitotic figure, slightly pleomorphic nuclei, and prominent nucleoli (J:172430)

• tumors show a range of differentiation between well- and moderately-differentiated hepatocellular carcinoma (J:172430)

• mice develop multifocal hepatocellular carcinoma within 5-8 weeks of age when doxycycline is removed at birth, showing invasive tumor cells in glandular and solid pattern infiltrating adjacent normal liver tissue (J:186226)

• in doxycycline-treated mice (J:190067)

• however, treatment with adeno-associated virus-expressing Mir122 suppresses tumorigenesis (J:190067)

decreased tumor growth/size ( J:190067 )

• doxycycline-treated mice infected with an adeno-associated virus-expressing Mir122 exhibit suppression of tumorigenesis tumor cell proliferation compared with control mice

liver/biliary system

increased liver tumor incidence ( J:93899 , J:172430 )

• following withdrawal of doxycycline, mice develop tumors with a latency of 12 weeks and all mice succumb to liver tumors within 2 weeks (J:93899)

• liver tumors that develop in mice after doxycycline withdrawal are invasive and metastasis into the thoracic cavity and lung parenchyma (J:93899)

• however, re-establishment of doxycycline-treatment produces rapid and sustained tumor regression (J:93899)

• repeated withdrawal and treatment with doxycyclineinduces and represses, respectively, tumor formation (J:93899)

increased hepatoblastoma incidence ( J:93899 )

• liver tumors that develop in mice after doxycycline withdrawal resemble hepatocellular carcinomas and/or hepatoblastomas

increased hepatocellular carcinoma incidence ( J:93899 , J:172430 , J:186226 , J:190067 )

• liver tumors that develop in mice after doxycycline withdrawal resemble hepatocellular carcinomas and/or hepatoblastomas (J:93899)

• tumors that form in mice after doxycycline withdrawal are composed of hepatocellular neoplasms characterized by sheets of cells with occasional mitotic figure, slightly pleomorphic nuclei, and prominent nucleoli (J:172430)

• tumors show a range of differentiation between well- and moderately-differentiated hepatocellular carcinoma (J:172430)

• mice develop multifocal hepatocellular carcinoma within 5-8 weeks of age when doxycycline is removed at birth, showing invasive tumor cells in glandular and solid pattern infiltrating adjacent normal liver tissue (J:186226)

• in doxycycline-treated mice (J:190067)

• however, treatment with adeno-associated virus-expressing Mir122 suppresses tumorigenesis (J:190067)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
colorectal cancer		DOID:9256	OMIM:114500	J:190067
hepatocellular carcinoma		DOID:684	OMIM:114550	J:93899 , J:172430 , J:186226