Phenotypes associated with this allele

• Allele Symbol: Tg(MMTV-rtTA)1Lach
• Allele Name: transgene insertion 1, Lewis A Chodosh
• Allele ID: MGI:3511875
• Summary: 15 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Brca1^tm2Cxd/Brca1^tm2Cxd Tg(MMTV-cre)4Mam/0 Tg(MMTV-rtTA)1Lach/0 Tg(tetO-Esr1)#Paf/0 Trp53^tm1Brd/Trp53^+	involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB	MGI:5297135
cn2	Stat5b^tm1Mam/Stat5b^tm1Mam Tg(MMTV-cre)1Mam/0 Tg(MMTV-rtTA)1Lach/0 Tg(tetO-Stat5a)#Mam/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:4847638
cn3	Stat5a^tm2Mam/Stat5a^tm2Mam Stat5b^tm1Mam/Stat5b^tm1Mam Tg(MMTV-cre)1Mam/0 Tg(MMTV-rtTA)1Lach/0 Tg(tetO-Stat5a)#Mam/0	involves: 129S6/SvEvTac * C57BL/6J * FVB/N	MGI:4847637
cx4	Tg(MMTV-rtTA)1Lach/0 Tg(tetO-PyVT,-cre)1Mul/0	FVB/N-Tg(MMTV-rtTA)1Lach Tg(tetO-PyVT,-cre)#Mul	MGI:5903421
cx5	Tg(MMTV-KRAS*G12V)3025Mrl/0 Tg(MMTV-rtTA)1Lach/0 Tg(tetO-MYC)1Lach/0	involves: C57BL/6 * FVB/N * SJL	MGI:5827761
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-IGF1R)1Ramo/0	involves: FVB	MGI:5432258
cx8	Tg(MMTV-rtTA)1Lach/0 Tg(TetO-Erbb2)1Lach/0	involves: FVB	MGI:5506798
cx9	Tg(MMTV-rtTA)1Lach/0 Tg(tetO-MYC)1Lach/0	involves: FVB	MGI:5432250
cx10	Tg(MMTV-rtTA)1Lach/0 Tg(tetO-Esr1)#Paf/0	involves: FVB/N	MGI:5296806
cx11	Tg(MMTV-rtTA)1Lach/0 Tg(tetO-PIK3CA*H1047R,-luc)2239Jjz/0	involves: FVB/N	MGI:5526972
cx12	Tg(MMTV-rtTA)1Lach/0 Tg(tetO-ERBB2)#Jjz/0	involves: FVB/N	MGI:5775603
cx13	Tg(MMTV-rtTA)1Lach/0 Tg(tetO-Kras2)12Hev/0	involves: FVB/N	MGI:5827756
cx14	Tg(MMTV-rtTA)1Lach/0 Tg(tetO-Kras2)12Hev/0 Tg(tetO-MYC)1Lach/0	involves: FVB/N	MGI:5827758
tg15	Tg(MMTV-rtTA)1Lach/0	involves: FVB/N	MGI:4821375

Genotype
MGI:5297135

cn1

• Allelic Composition: Brca1^tm2Cxd/Brca1^tm2Cxd; Tg(MMTV-cre)4Mam/0; Tg(MMTV-rtTA)1Lach/0; Tg(tetO-Esr1)#Paf/0; Trp53^tm1Brd/Trp53⁺
• Genetic Background: involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 * FVB

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

endocrine/exocrine glands

mammary gland alveolar hyperplasia ( J:132088 )

♀ • mutants develop hyperplastic alveolar nodules

increased mammary gland tumor incidence ( J:132088 )

• 100% of mutants develop invasive mammary cancer

• some cancers are Esr1-negative while others are Esr1-positive

neoplasm

increased mammary gland tumor incidence ( J:132088 )

• 100% of mutants develop invasive mammary cancer

• some cancers are Esr1-negative while others are Esr1-positive

preneoplasia ( J:132088 )

• mutants develop mammary gland preneoplasia

• some preneoplasia are Esr1-negative while others are Esr1-positive

integument

mammary gland alveolar hyperplasia ( J:132088 )

♀ • mutants develop hyperplastic alveolar nodules

increased mammary gland tumor incidence ( J:132088 )

• 100% of mutants develop invasive mammary cancer

• some cancers are Esr1-negative while others are Esr1-positive

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary breast ovarian cancer syndrome		DOID:5683		J:132088

Genotype
MGI:4847638

cn2

• Allelic Composition: Stat5b^tm1Mam/Stat5b^tm1Mam; Tg(MMTV-cre)1Mam/0; Tg(MMTV-rtTA)1Lach/0; Tg(tetO-Stat5a)#Mam/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:153755 )

N • with doxycycline food during pregnancy female mice develop functional mammary glands during pregnancy and are able to feed their pups

N • expanded alveoli lined with differentiated secretory cells, with proteinaceous material and lipid droplets in the lumen after doxycycline treatment

N • formation of alveolar structures and functional differentiation of luminal cells after doxycycline treatment

N • the mutant mice generate CD61+ luminal progenitor cells during pregnancy to a similar extent as Stat5a/Stat5b^tm2Mam control mice

reproductive system

reproductive system phenotype ( J:153755 )

N • with doxycycline food during pregnancy female mice develop functional mammary glands during pregnancy and are able to feed their pups

N • expanded alveoli lined with differentiated secretory cells, with proteinaceous material and lipid droplets in the lumen after doxycycline treatment

N • formation of alveolar structures and functional differentiation of luminal cells after doxycycline treatment

N • the mutant mice generate CD61+ luminal progenitor cells during pregnancy to a similar extent as Stat5a/Stat5b^tm2Mam control mice

Genotype
MGI:4847637

cn3

• Allelic Composition: Stat5a^tm2Mam/Stat5a^tm2Mam; Stat5b^tm1Mam/Stat5b^tm1Mam; Tg(MMTV-cre)1Mam/0; Tg(MMTV-rtTA)1Lach/0; Tg(tetO-Stat5a)#Mam/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * FVB/N

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:153755 )

N • with doxycycline food during pregnancy female mice develop functional mammary glands during pregnancy and are able to feed their pups

N • expanded alveoli lined with differentiated secretory cells, with proteinaceous material and lipid droplets in the lumen after doxycycline treatment

N • formation of alveolar structures and functional differentiation of luminal cells after doxycycline treatment

N • the mutant mice generate CD61+ luminal progenitor cells during pregnancy to a similar extent as Stat5a/Stat5b^tm2Mam control mice

reproductive system

reproductive system phenotype ( J:153755 )

N • with doxycycline food during pregnancy female mice develop functional mammary glands during pregnancy and are able to feed their pups

N • expanded alveoli lined with differentiated secretory cells, with proteinaceous material and lipid droplets in the lumen after doxycycline treatment

N • formation of alveolar structures and functional differentiation of luminal cells after doxycycline treatment

N • the mutant mice generate CD61+ luminal progenitor cells during pregnancy to a similar extent as Stat5a/Stat5b^tm2Mam control mice

Genotype
MGI:5903421

cx4

• Allelic Composition: Tg(MMTV-rtTA)1Lach/0; Tg(tetO-PyVT,-cre)1Mul/0
• Genetic Background: FVB/N-Tg(MMTV-rtTA)1Lach Tg(tetO-PyVT,-cre)#Mul

neoplasm

increased mammary adenocarcinoma incidence ( J:231983 )

• mammary tumors in doxycycline treated virgin females progress to carcinoma

increased mammary gland tumor incidence in virgin females ( J:231983 )

• 74.4% of virgin females induced with doxycycline between 8 and 16 weeks of age develop multifocal mammary tumors within 16 days of induction and a further 12.8% of females develop tumors between 17 and 365 days post-induction

• 12.8% of virgin females induced with doxycycline remain tumor-free after 1 year of induction

• average tumor onset is 22 days post doxycycline induction

• mammary glands of doxycycline treated mice show all stages of tumorigenesis, progressing from hyperplasia, to mammary intraepithelial neoplasia/adenoma, and finally to early and late carcinoma

• discontinuing doxycycline treatment in mice bearing end-stage mammary tumors results in tumor regression but eventually recurrence of doxycycline-independent masses is seen

increased metastatic potential ( J:231983 )

• mammary tumors from doxycycline induced mice metastasize to the lungs

• however, no correlation between the extent of metastasis and tumor burden is seen

integument

increased mammary adenocarcinoma incidence ( J:231983 )

• mammary tumors in doxycycline treated virgin females progress to carcinoma

increased mammary gland tumor incidence in virgin females ( J:231983 )

• 74.4% of virgin females induced with doxycycline between 8 and 16 weeks of age develop multifocal mammary tumors within 16 days of induction and a further 12.8% of females develop tumors between 17 and 365 days post-induction

• 12.8% of virgin females induced with doxycycline remain tumor-free after 1 year of induction

• average tumor onset is 22 days post doxycycline induction

• mammary glands of doxycycline treated mice show all stages of tumorigenesis, progressing from hyperplasia, to mammary intraepithelial neoplasia/adenoma, and finally to early and late carcinoma

• discontinuing doxycycline treatment in mice bearing end-stage mammary tumors results in tumor regression but eventually recurrence of doxycycline-independent masses is seen

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:231983 )

• mammary tumors in doxycycline treated virgin females progress to carcinoma

increased mammary gland tumor incidence in virgin females ( J:231983 )

• 74.4% of virgin females induced with doxycycline between 8 and 16 weeks of age develop multifocal mammary tumors within 16 days of induction and a further 12.8% of females develop tumors between 17 and 365 days post-induction

• 12.8% of virgin females induced with doxycycline remain tumor-free after 1 year of induction

• average tumor onset is 22 days post doxycycline induction

• mammary glands of doxycycline treated mice show all stages of tumorigenesis, progressing from hyperplasia, to mammary intraepithelial neoplasia/adenoma, and finally to early and late carcinoma

• discontinuing doxycycline treatment in mice bearing end-stage mammary tumors results in tumor regression but eventually recurrence of doxycycline-independent masses is seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:231983

Genotype
MGI:5827761

cx5

• Allelic Composition: Tg(MMTV-KRAS*G12V)3025Mrl/0; Tg(MMTV-rtTA)1Lach/0; Tg(tetO-MYC)1Lach/0
• Genetic Background: involves: C57BL/6 * FVB/N * SJL

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, tumors become smaller within 5-7 days of withdrawal, however, none of the palpable tumors regress completely after 3 weeks and begin to regrow within 3-6 weeks

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, tumors become smaller within 5-7 days of withdrawal, however, none of the palpable tumors regress completely after 3 weeks and begin to regrow within 3-6 weeks

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, tumors become smaller within 5-7 days of withdrawal, however, none of the palpable tumors regress completely after 3 weeks and begin to regrow within 3-6 weeks

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

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:5432258

cx7

• Allelic Composition: Tg(MMTV-rtTA)1Lach/0; Tg(tetO-IGF1R)1Ramo/0
• Genetic Background: involves: FVB

neoplasm

increased mammary gland tumor incidence ( J:121069 )

• mutants maintained on doxycycline for an extended period of time develop mammary tumors with an average latency of 78 days

• doxycycline-treated mutants typically develop one or two tumors in the first or second/third mammary glands with hyperplastic nodules in the other mammary glands

• small mammary lesions are primarily composed of solid sheets of tumor cells with sparse stroma

• larger tumors are more heterogeneous in appearance, with tumors displaying features of adenosquamous carcinoma, adenomyoepithelioloma, and glandular adenocarcinoma

increased mammary adenocarcinoma incidence ( J:121069 )

• larger tumors display features of adenosquamous carcinoma and glandular adenocarcinoma

endocrine/exocrine glands

abnormal mammary gland development ( J:121069 )

♀ • 55 day old mutants induced with doxycycline beginning at 21 days of age exhibit impaired mammary ductal development

abnormal branching of the mammary ductal tree ( J:121069 )

♀ • 55 day old mutants induced with doxycycline beginning at 21 days of age show a delay in ductal elongation and in some cases the duct remains behind in the lymph node compared to controls in which ductal structure almost completely fills the mammary fat pad

abnormal mammary gland epithelium morphology ( J:121069 )

♀ • 55 day old mutants induced with doxycycline beginning at 21 days of age exhibit mammary epithelial hyperplasia

increased mammary gland tumor incidence ( J:121069 )

• mutants maintained on doxycycline for an extended period of time develop mammary tumors with an average latency of 78 days

• doxycycline-treated mutants typically develop one or two tumors in the first or second/third mammary glands with hyperplastic nodules in the other mammary glands

• small mammary lesions are primarily composed of solid sheets of tumor cells with sparse stroma

• larger tumors are more heterogeneous in appearance, with tumors displaying features of adenosquamous carcinoma, adenomyoepithelioloma, and glandular adenocarcinoma

increased mammary adenocarcinoma incidence ( J:121069 )

• larger tumors display features of adenosquamous carcinoma and glandular adenocarcinoma

mammary gland hyperplasia ( J:121069 )

♀ • 55 day old mutants induced with doxycycline beginning at 21 days of age exhibit mammary epithelial hyperplasia

integument

abnormal mammary gland development ( J:121069 )

♀ • 55 day old mutants induced with doxycycline beginning at 21 days of age exhibit impaired mammary ductal development

abnormal branching of the mammary ductal tree ( J:121069 )

♀ • 55 day old mutants induced with doxycycline beginning at 21 days of age show a delay in ductal elongation and in some cases the duct remains behind in the lymph node compared to controls in which ductal structure almost completely fills the mammary fat pad

abnormal mammary gland epithelium morphology ( J:121069 )

♀ • 55 day old mutants induced with doxycycline beginning at 21 days of age exhibit mammary epithelial hyperplasia

increased mammary gland tumor incidence ( J:121069 )

• mutants maintained on doxycycline for an extended period of time develop mammary tumors with an average latency of 78 days

• doxycycline-treated mutants typically develop one or two tumors in the first or second/third mammary glands with hyperplastic nodules in the other mammary glands

• small mammary lesions are primarily composed of solid sheets of tumor cells with sparse stroma

• larger tumors are more heterogeneous in appearance, with tumors displaying features of adenosquamous carcinoma, adenomyoepithelioloma, and glandular adenocarcinoma

increased mammary adenocarcinoma incidence ( J:121069 )

• larger tumors display features of adenosquamous carcinoma and glandular adenocarcinoma

mammary gland hyperplasia ( J:121069 )

♀ • 55 day old mutants induced with doxycycline beginning at 21 days of age exhibit mammary epithelial hyperplasia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:121069

Genotype
MGI:5506798

cx8

• Allelic Composition: Tg(MMTV-rtTA)1Lach/0; Tg(TetO-Erbb2)1Lach/0
• Genetic Background: involves: FVB

neoplasm

increased mammary adenocarcinoma incidence ( J:81083 )

• mice treated with doxycycline for 21 days develop invasive mammary carcinomas

• chronic treatment with doxycycline results in rapid development of multiple mammary tumors with 100% penetrance and a latency of 6 weeks

• mammary tumors are invasive solid nodular carcinomas

• withdrawal of doxycycline from chronically induced mutants results in full regression of tumors to a nonpalpable state in 94% of mice; a decrease in cell proliferation and increase in cell apoptosis is seen during regression

• mice in which doxycycline withdrawal leads to complete regression of tumors show tumor recurrence in the absence of doxycycline after an average of 153 +/- 93 days off doxycycline

increased metastatic potential ( J:81083 )

• some mutants treated with doxycycline develop pulmonary metastases (solid pulmonary nodules on the pleural surface); these mice show hunched posture, ruffled fur, labored breathing and die within one week

• pulmonary metastases have features of mammary epithelial carcinomas

• withdrawal of doxycycline from chronically induced mutants with pulmonary metastasis results in regression of primary mammary tumors and resolution of the respiratory phenotype

mortality/aging

premature death ( J:81083 )

• mice that develop pulmonary metastases following chronic doxycycline treatment die within one week of developing a hunched posture and labored breathing

endocrine/exocrine glands

mammary gland duct hyperplasia ( J:81083 )

• mice treated with doxycycline for 4 days exhibit hyperplastic abnormalities in the mammary ductal trees

increased mammary adenocarcinoma incidence ( J:81083 )

• mice treated with doxycycline for 21 days develop invasive mammary carcinomas

• chronic treatment with doxycycline results in rapid development of multiple mammary tumors with 100% penetrance and a latency of 6 weeks

• mammary tumors are invasive solid nodular carcinomas

• withdrawal of doxycycline from chronically induced mutants results in full regression of tumors to a nonpalpable state in 94% of mice; a decrease in cell proliferation and increase in cell apoptosis is seen during regression

• mice in which doxycycline withdrawal leads to complete regression of tumors show tumor recurrence in the absence of doxycycline after an average of 153 +/- 93 days off doxycycline

integument

mammary gland duct hyperplasia ( J:81083 )

• mice treated with doxycycline for 4 days exhibit hyperplastic abnormalities in the mammary ductal trees

increased mammary adenocarcinoma incidence ( J:81083 )

• mice treated with doxycycline for 21 days develop invasive mammary carcinomas

• chronic treatment with doxycycline results in rapid development of multiple mammary tumors with 100% penetrance and a latency of 6 weeks

• mammary tumors are invasive solid nodular carcinomas

• withdrawal of doxycycline from chronically induced mutants results in full regression of tumors to a nonpalpable state in 94% of mice; a decrease in cell proliferation and increase in cell apoptosis is seen during regression

• mice in which doxycycline withdrawal leads to complete regression of tumors show tumor recurrence in the absence of doxycycline after an average of 153 +/- 93 days off doxycycline

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:81083

Genotype
MGI:5432250

cx9

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

neoplasm

increased mammary gland tumor incidence ( J:67498 , J:133578 )

♀ • chronically doxycycline induced females develop mammary tumors with high penetrance (86%) following an average of 22 weeks of induction (J:67498)

♀ • mice fed doxycycline after weaning develop solitary mammary tumors with a median latency of 26 weeks after induction (J:133578)

increased mammary adenocarcinoma incidence ( J:67498 )

♀ • mammary tumors in chronically doxycycline induced females are invasive mammary adenocarcinomas

♀ • withdrawal of doxycycline from chronically induced tumor-bearing mutants results in rapid regression of a subset of invasive mammary adenocarcinomas (14 days) but another subset of tumors decrease in size but then resume growth

♀ • tumors that continue to grow after doxycycline removal show undetectable expression of the MYC transgene but increased endogenous Myc expression and exhibit mutations in Kras or Nras

integument

increased mammary gland epithelial cell proliferation ( J:67498 )

♀ • mammary epithelium of mutants induced with doxycycline exhibits increased proliferation

abnormal mammary gland morphology ( J:67498 )

♀ • mammary glands of mutants induced with doxycycline for 4 months exhibit atypical lobuloalveolar growths (dysplasia)

abnormal mammary gland epithelium morphology ( J:67498 )

♀ • non-tumor bearing mammary glands of mutants induced with doxycycline for 30 weeks (chronically induced) exhibit numerous epithelial hyperplasts and dysplasts, however when doxycycline is withdrawn for 12 weeks, most epithelial ducts appear normal

increased mammary gland tumor incidence ( J:67498 , J:133578 )

♀ • chronically doxycycline induced females develop mammary tumors with high penetrance (86%) following an average of 22 weeks of induction (J:67498)

♀ • mice fed doxycycline after weaning develop solitary mammary tumors with a median latency of 26 weeks after induction (J:133578)

increased mammary adenocarcinoma incidence ( J:67498 )

♀ • mammary tumors in chronically doxycycline induced females are invasive mammary adenocarcinomas

♀ • withdrawal of doxycycline from chronically induced tumor-bearing mutants results in rapid regression of a subset of invasive mammary adenocarcinomas (14 days) but another subset of tumors decrease in size but then resume growth

♀ • tumors that continue to grow after doxycycline removal show undetectable expression of the MYC transgene but increased endogenous Myc expression and exhibit mutations in Kras or Nras

mammary gland hyperplasia ( J:67498 )

♀ • mammary glands of mutants induced with doxycycline for 30 days are hyperplastic

♀ • mammary glands of mutants induced with doxycycline for 4 months exhibit focal hyperplasia

increased mammary gland apoptosis ( J:67498 )

♀ • mammary epithelium of mutants induced with doxycycline exhibits increased apoptosis

endocrine/exocrine glands

increased mammary gland epithelial cell proliferation ( J:67498 )

♀ • mammary epithelium of mutants induced with doxycycline exhibits increased proliferation

abnormal mammary gland morphology ( J:67498 )

♀ • mammary glands of mutants induced with doxycycline for 4 months exhibit atypical lobuloalveolar growths (dysplasia)

abnormal mammary gland epithelium morphology ( J:67498 )

♀ • non-tumor bearing mammary glands of mutants induced with doxycycline for 30 weeks (chronically induced) exhibit numerous epithelial hyperplasts and dysplasts, however when doxycycline is withdrawn for 12 weeks, most epithelial ducts appear normal

increased mammary gland tumor incidence ( J:67498 , J:133578 )

♀ • chronically doxycycline induced females develop mammary tumors with high penetrance (86%) following an average of 22 weeks of induction (J:67498)

♀ • mice fed doxycycline after weaning develop solitary mammary tumors with a median latency of 26 weeks after induction (J:133578)

increased mammary adenocarcinoma incidence ( J:67498 )

♀ • mammary tumors in chronically doxycycline induced females are invasive mammary adenocarcinomas

♀ • withdrawal of doxycycline from chronically induced tumor-bearing mutants results in rapid regression of a subset of invasive mammary adenocarcinomas (14 days) but another subset of tumors decrease in size but then resume growth

♀ • tumors that continue to grow after doxycycline removal show undetectable expression of the MYC transgene but increased endogenous Myc expression and exhibit mutations in Kras or Nras

mammary gland hyperplasia ( J:67498 )

♀ • mammary glands of mutants induced with doxycycline for 30 days are hyperplastic

♀ • mammary glands of mutants induced with doxycycline for 4 months exhibit focal hyperplasia

increased mammary gland apoptosis ( J:67498 )

♀ • mammary epithelium of mutants induced with doxycycline exhibits increased apoptosis

cellular

increased mammary gland epithelial cell proliferation ( J:67498 )

♀ • mammary epithelium of mutants induced with doxycycline exhibits increased proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:67498 , J:133578

Genotype
MGI:5296806

cx10

• Allelic Composition: Tg(MMTV-rtTA)1Lach/0; Tg(tetO-Esr1)#Paf/0
• Genetic Background: involves: FVB/N

endocrine/exocrine glands

abnormal mammary gland morphology ( J:96383 )

♀ • exposure to exogenous estrogen does not increase or change the prevalence of ductal abnormalities, proliferative disease or ductal carcinoma in situ

♀ • neither hyperplasia nor ductal carcinoma in situ regress within a 2-week period following doxycycline treatment in 4 month old mutants

♀ • ovariectomized mice do not show ductal hyperplasia, ductal carcinoma in situ or other ductal abnormalities

♀ • mutants which were treated with doxycycline at 3 weeks of age to inhibit Esr1 expression exhibit normal mammary gland development

abnormal mammary gland epithelium morphology ( J:96383 )

♀ • rates of mammary epithelial cell proliferation are increased compared to controls

abnormal mammary gland duct morphology ( J:96383 )

♀ • at 4 months of age, mutants show abnormal mammary ductal structures, including lateral budding, dilated ducts, and abnormal branching

abnormal branching of the mammary ductal tree ( J:96383 )

♀ • at 4 months of age, mutants show lateral budding and abnormal branching of mammary gland ducts

mammary gland duct hyperplasia ( J:96383 )

♀ • 33% and 36% of mutants at 2 and 4 months of age, respectively, show ductal hyperplasia

abnormal mammary gland lobule morphology ( J:96383 )

♀ • 52% of mutants at 4 months of age show lobular hyperplasia

mammary gland alveolar hyperplasia ( J:96383 )

♀ • 12 month old mice display hyperplastic alveolar nodules with increased frequency of mitotic figures within the hyperplasias

increased mammary gland ductal carcinoma incidence ( J:96383 )

• 17% and 21% of mutants at 2 and 4 months of age, respectively, develop ductal carcinoma in situ

neoplasm

increased mammary gland ductal carcinoma incidence ( J:96383 )

• 17% and 21% of mutants at 2 and 4 months of age, respectively, develop ductal carcinoma in situ

integument

abnormal mammary gland morphology ( J:96383 )

♀ • exposure to exogenous estrogen does not increase or change the prevalence of ductal abnormalities, proliferative disease or ductal carcinoma in situ

♀ • neither hyperplasia nor ductal carcinoma in situ regress within a 2-week period following doxycycline treatment in 4 month old mutants

♀ • ovariectomized mice do not show ductal hyperplasia, ductal carcinoma in situ or other ductal abnormalities

♀ • mutants which were treated with doxycycline at 3 weeks of age to inhibit Esr1 expression exhibit normal mammary gland development

abnormal mammary gland epithelium morphology ( J:96383 )

♀ • rates of mammary epithelial cell proliferation are increased compared to controls

abnormal mammary gland duct morphology ( J:96383 )

♀ • at 4 months of age, mutants show abnormal mammary ductal structures, including lateral budding, dilated ducts, and abnormal branching

abnormal branching of the mammary ductal tree ( J:96383 )

♀ • at 4 months of age, mutants show lateral budding and abnormal branching of mammary gland ducts

mammary gland duct hyperplasia ( J:96383 )

♀ • 33% and 36% of mutants at 2 and 4 months of age, respectively, show ductal hyperplasia

abnormal mammary gland lobule morphology ( J:96383 )

♀ • 52% of mutants at 4 months of age show lobular hyperplasia

mammary gland alveolar hyperplasia ( J:96383 )

♀ • 12 month old mice display hyperplastic alveolar nodules with increased frequency of mitotic figures within the hyperplasias

increased mammary gland ductal carcinoma incidence ( J:96383 )

• 17% and 21% of mutants at 2 and 4 months of age, respectively, develop ductal carcinoma in situ

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:96383

Genotype
MGI:5526972

cx11

• Allelic Composition: Tg(MMTV-rtTA)1Lach/0; Tg(tetO-PIK3CA*H1047R,-luc)2239Jjz/0
• Genetic Background: involves: FVB/N

neoplasm

increased mammary gland tumor incidence ( J:175839 )

♀ • females treated with doxycycline for 4 weeks exhibit increased mammary ductal side-branching and enlarged focal nodular structures filled with hyperproliferative cells characteristic of early neoplastic lesions

♀ • chronic doxycycline induction results in development of mammary tumors with 95% penetrance and a mean latency of 7 months

♀ • withdrawal of doxycycline from females bearing tumors results in tumor regression during the first week after doxycycline removal, with a reduction in cellular proliferation and increase in apoptosis

♀ • withdrawal of doxycycline from females bearing tumors for up to 6 months results in 33% of tumors showing complete regression to a nonpalpable state within 1-2 months after doxycycline withdrawal with no regrowth, while 64% of tumors partially regress but then resume growth without doxycline and 3% partially regress but do not resume growth

increased mammary adenocarcinoma incidence ( J:175839 )

♀ • mammary tumors of doxycycline treated females include adenocarcinomas and adenosquamous carcinomas

integument

increased mammary gland tumor incidence ( J:175839 )

♀ • females treated with doxycycline for 4 weeks exhibit increased mammary ductal side-branching and enlarged focal nodular structures filled with hyperproliferative cells characteristic of early neoplastic lesions

♀ • chronic doxycycline induction results in development of mammary tumors with 95% penetrance and a mean latency of 7 months

♀ • withdrawal of doxycycline from females bearing tumors results in tumor regression during the first week after doxycycline removal, with a reduction in cellular proliferation and increase in apoptosis

♀ • withdrawal of doxycycline from females bearing tumors for up to 6 months results in 33% of tumors showing complete regression to a nonpalpable state within 1-2 months after doxycycline withdrawal with no regrowth, while 64% of tumors partially regress but then resume growth without doxycline and 3% partially regress but do not resume growth

increased mammary adenocarcinoma incidence ( J:175839 )

♀ • mammary tumors of doxycycline treated females include adenocarcinomas and adenosquamous carcinomas

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:175839 )

♀ • females treated with doxycycline for 4 weeks exhibit increased mammary ductal side-branching and enlarged focal nodular structures filled with hyperproliferative cells characteristic of early neoplastic lesions

♀ • chronic doxycycline induction results in development of mammary tumors with 95% penetrance and a mean latency of 7 months

♀ • withdrawal of doxycycline from females bearing tumors results in tumor regression during the first week after doxycycline removal, with a reduction in cellular proliferation and increase in apoptosis

♀ • withdrawal of doxycycline from females bearing tumors for up to 6 months results in 33% of tumors showing complete regression to a nonpalpable state within 1-2 months after doxycycline withdrawal with no regrowth, while 64% of tumors partially regress but then resume growth without doxycline and 3% partially regress but do not resume growth

increased mammary adenocarcinoma incidence ( J:175839 )

♀ • mammary tumors of doxycycline treated females include adenocarcinomas and adenosquamous carcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:175839

Genotype
MGI:5775603

cx12

• Allelic Composition: Tg(MMTV-rtTA)1Lach/0; Tg(tetO-ERBB2)#Jjz/0
• Genetic Background: involves: FVB/N

endocrine/exocrine glands

abnormal branching of the mammary ductal tree ( J:231766 )

♀ • mice treated with doxycycline for 2 weeks exhibit increased lateral branching and ductal ectasia of adult mammary ductal trees

increased mammary adenocarcinoma incidence ( J:231766 )

♀ • doxycycline treatment beginning at 8 weeks of age results in the development of mammary tumors with 100% penetrance and median latency of about 2 months

♀ • tumors are consistent with moderate to poorly differentiated adenocarcinoma admixed with foci of ductal carcinoma in situ resembling human HER2-positive breast cancers

♀ • tumor cell apoptosis and reduced tumor cellularity are seen within 24-48 hours of doxycycline removal, followed by tumor regression within 4-5 days

♀ • lapatinib treatment results in arrest of tumor growth and/or regression

♀ • about 2/3 of mice develop a recurrent mammary gland tumor when doxycycline is withdrawn; recurrent tumors do not express ERBB2 and have different expression profiles than primary tumors

♀ • trastuzumab treatment results in in tumor regression and subsequent regrowth in two tumors despite continued therapy, indicating development of trastuzumab-resistant tumors

♀ • primary tumor cells treated with both lapatinib and trastuzumab exhibit some growth inhibition which is enhanced further with the addition of the CDK4/6 inhibitor abemaciclib

integument

abnormal branching of the mammary ductal tree ( J:231766 )

♀ • mice treated with doxycycline for 2 weeks exhibit increased lateral branching and ductal ectasia of adult mammary ductal trees

increased mammary adenocarcinoma incidence ( J:231766 )

♀ • doxycycline treatment beginning at 8 weeks of age results in the development of mammary tumors with 100% penetrance and median latency of about 2 months

♀ • tumors are consistent with moderate to poorly differentiated adenocarcinoma admixed with foci of ductal carcinoma in situ resembling human HER2-positive breast cancers

♀ • tumor cell apoptosis and reduced tumor cellularity are seen within 24-48 hours of doxycycline removal, followed by tumor regression within 4-5 days

♀ • lapatinib treatment results in arrest of tumor growth and/or regression

♀ • about 2/3 of mice develop a recurrent mammary gland tumor when doxycycline is withdrawn; recurrent tumors do not express ERBB2 and have different expression profiles than primary tumors

♀ • trastuzumab treatment results in in tumor regression and subsequent regrowth in two tumors despite continued therapy, indicating development of trastuzumab-resistant tumors

♀ • primary tumor cells treated with both lapatinib and trastuzumab exhibit some growth inhibition which is enhanced further with the addition of the CDK4/6 inhibitor abemaciclib

neoplasm

increased mammary adenocarcinoma incidence ( J:231766 )

♀ • doxycycline treatment beginning at 8 weeks of age results in the development of mammary tumors with 100% penetrance and median latency of about 2 months

♀ • tumors are consistent with moderate to poorly differentiated adenocarcinoma admixed with foci of ductal carcinoma in situ resembling human HER2-positive breast cancers

♀ • tumor cell apoptosis and reduced tumor cellularity are seen within 24-48 hours of doxycycline removal, followed by tumor regression within 4-5 days

♀ • lapatinib treatment results in arrest of tumor growth and/or regression

♀ • about 2/3 of mice develop a recurrent mammary gland tumor when doxycycline is withdrawn; recurrent tumors do not express ERBB2 and have different expression profiles than primary tumors

♀ • trastuzumab treatment results in in tumor regression and subsequent regrowth in two tumors despite continued therapy, indicating development of trastuzumab-resistant tumors

♀ • primary tumor cells treated with both lapatinib and trastuzumab exhibit some growth inhibition which is enhanced further with the addition of the CDK4/6 inhibitor abemaciclib

increased metastatic potential ( J:231766 )

♀ • 80% of mice show lung metastases after 16 weeks of sustained doxycycline induction

♀ • lung metastases are seen in only 15% of mice induced for 16 weeks and subsequently maintained on a doxycycline-free diet for 4 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:231766

Genotype
MGI:5827756

cx13

• 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:5827758

cx14

• 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:4821375

tg15

• Allelic Composition: Tg(MMTV-rtTA)1Lach/0
• Genetic Background: involves: FVB/N

reproductive system

reproductive system phenotype ( J:75048 )

N • mice exhibit normal mammary gland development