Phenotypes associated with this allele

• Allele Symbol: Tg(Scgb1a1-rtTA)1Jaw
• Allele Name: transgene insertion 1, Jeffrey A Whitsett
• Allele ID: MGI:2445707
• Summary: 30 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Scgb1a1-rtTA)1Jaw/0	involves: 129S4/SvJae	MGI:4368025
cn2	Col1a1^tm5(tetO-GFP/RNAi:Cdkn2a)Slowe/Col1a1^+ Gt(ROSA)26Sor^tm1(Luc)Kael/Gt(ROSA)26Sor^tm1(rtTA*M2)Jae Kras^tm4Tyj/Kras^+ Tg(Scgb1a1-rtTA)1Jaw/0	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:4999988
cn3	Foxa2^tm1Khk/Foxa2^tm1Khk Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-cre)1Jaw/0	Not Specified	MGI:3036450
cx4	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Aimp1)29872Mcla/0	involves: 129 * C57BL/6	MGI:5604244
cx5	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-TGFA)22.1Kor/0	involves: 129 * C57BL/6	MGI:6275555
cx6	Col1a1^tm1(tetO-EML4/ALK)Kkw/Col1a1^+ Tg(Scgb1a1-rtTA)1Jaw/0	involves: 129 * C57BL/6	MGI:5527337
cx7	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-IL1B)KBry/0	involves: 129 * C57BL/6	MGI:5444503
cx8	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-MYC)36Bop/0	involves: 129 * C57BL/6	MGI:4946282
cx9	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-CTGF)#Swu/0	involves: 129 * C57BL/6 * C57BL/6J	MGI:5473719
cx10	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*L858R)#Hev/0	involves: 129 * C57BL/6 * CBA	MGI:5634289
cx11	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-IGF1R)1Ramo/0	involves: 129 * C57BL/6 * FVB	MGI:7266256
cx12	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*T790M*L858R)19Kkw/0	involves: 129 * C57BL/6 * FVB/N	MGI:5781131
cx13	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Spdef)1Jaw/0	involves: 129 * C57BL/6 * FVB/N	MGI:4410330
cx14	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-PIK3CA*H1047R)13Lca/0	involves: 129 * C57BL/6 * FVB/N	MGI:3834442
cx15	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Kras2)12Hev/0	involves: 129 * C57BL/6 * FVB/N	MGI:5912341
cx16	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-PTPN11*E76K)#Jiwu/0	involves: 129 * C57BL/6 * FVB/N	MGI:5688300
cx17	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*T790M)8Paow/0	involves: 129 * C57BL/6 * FVB/N	MGI:5705252
cx18	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*T790M*L858R)51Paow/0	involves: 129 * C57BL/6 * FVB/N	MGI:5705253
cx19	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*)#Kkw/0	involves: 129 * C57BL/6 * FVB/N	MGI:6256808
cx20	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-TGFA)22.1Kor/0	involves: 129 * C57BL/6 * FVB/NJ	MGI:6275557
cx21	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Kras2)12Hev/0	involves: 129 * C57BL/6J * FVB/N * SJL	MGI:5912294
cx22	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Kras2)12Hev/0 Trp53^tm1Tyj/Trp53^+	involves: 129S2/SvPas * C57BL/6 * FVB/N	MGI:5912344
cx23	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*L858R)57Hev/0	involves: C57BL/6 * CBA	MGI:3690090
cx24	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*delta19)11Hev/0	involves: C57BL/6 * CBA	MGI:3690458
cx25	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*L858R)56Hev/0	involves: C57BL/6 * CBA	MGI:3690087
cx26	Tg(tetO-Plau)1Ths/0 Tg(Scgb1a1-rtTA)1Jaw/0	involves: C57BL/6 * SJL	MGI:2652187
cx27	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-ERBB2*)5BKkw/0	involves: FVB/N	MGI:5912489
cx28	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-ERBB2*)26Kkw/0	involves: FVB/N	MGI:5912488
cx29	Tg(tetO-Vegfa)90Ala/? Tg(Scgb1a1-rtTA)1Jaw/?	involves: FVB/N	MGI:3586366
cx30	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO/CMV-KRAS*G12C)9.1Msmi/0	involves: FVB/N	MGI:3693292

Genotype
MGI:4368025

cn1

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Scgb1a1-rtTA)1Jaw/0
• Genetic Background: involves: 129S4/SvJae

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

neoplasm

abnormal tumor morphology ( J:154041 )

• infiltrating inflammatory cells recruited to tumors in which NF-kB has been inhibited

• tumorigenesis is initiated by infection with lentiviruses expressing Cre and Nfkbia lentiviruses

decreased tumor growth/size ( J:154041 )

• doxycycline (Dox)-mediated induction of Nfkbia expression specifically in the tumor cells starting at 16 weeks after tumor initiation results in a significantly diminished tumour growth rate

• tumorigenesis is initiated by infection with lentiviruses expressing Cre and Nfkbia lentiviruses

decreased incidence of induced tumors ( J:154041 )

• doxycycline (Dox)-mediated induction of Nfkbia expression specifically in the tumor cells leads to a significant impairment of tumour development

• tumorigenesis is initiated by infection with lentiviruses expressing Cre and Nfkbia lentiviruses

Genotype
MGI:4999988

cn2

• Allelic Composition: Col1a1^{tm5(tetO-GFP/RNAi:Cdkn2a)Slowe}/Col1a1⁺; Gt(ROSA)26Sor^tm1(Luc)Kael/Gt(ROSA)26Sor^{tm1(rtTA*M2)Jae}; Kras^tm4Tyj/Kras⁺; Tg(Scgb1a1-rtTA)1Jaw/0
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

mortality/aging

premature death ( J:171191 )

• mice treated with a cre-expressing adenovirus and treated with doxycycline exhibit reduced survival compared with control mice

neoplasm

increased tumor incidence ( J:171191 )

• mice treated with a cre-expressing adenovirus and treated with doxycycline exhibit increased tumor incidence (size and number) in the lungs with rare noninvasive lung adenomas compared with control mice

• however, mice treated with a cre-expressing adenovirus and treated with doxycycline exhibit tumor regression after doxycycline removal

increased lung adenoma incidence ( J:171191 )

• in mice treated with a cre-expressing adenovirus and treated with doxycycline

respiratory system

increased lung adenoma incidence ( J:171191 )

• in mice treated with a cre-expressing adenovirus and treated with doxycycline

respiratory distress ( J:171191 )

• rapid shallow breathing in mice treated with a cre-expressing adenovirus and treated with doxycycline

growth/size/body

cachexia ( J:171191 )

• in mice treated with a cre-expressing adenovirus and treated with doxycycline

Genotype
MGI:3036450

cn3

• Allelic Composition: Foxa2^tm1Khk/Foxa2^tm1Khk; Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-cre)1Jaw/0
• Genetic Background: Not Specified

immune system

immune system phenotype ( J:88601 )

N • no increase in the number of neutrophils or macrophages in mice treated with doxycycline from E0 through P16

respiratory system

increased respiratory mucosa goblet cell number ( J:88601 )

• goblet cell hyperplasia, associated with the accumulation of both neutral and acidic mucins, in the larger airways of mice treated with doxycycline from E0 through P16

• neither airspace nor alveolar morphological abnormalities were detected

abnormal respiratory mechanics ( J:88601 )

increased airway resistance ( J:88601 )

• increased in mice treated with doxycycline

decreased lung compliance ( J:88601 )

• decreased in mice treated with doxycycline

Genotype
MGI:5604244

cx4

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-Aimp1)29872Mcla/0
• Genetic Background: involves: 129 * C57BL/6

cellular

increased lung endothelial cell apoptosis ( J:173904 )

• 3 fold increase in caspase 3 activity in lung alveolar cells is measured as early as 4 weeks after doxycycline (dox) induction

hematopoietic system

increased macrophage cell number ( J:173904 )

• 28 weeks of doxycycline induction results in an increase in the number of alveolar macrophages in bronchoalveolar lavage fluid (BALF) and lung parenchyma from lung lysates

immune system

increased macrophage cell number ( J:173904 )

• 28 weeks of doxycycline induction results in an increase in the number of alveolar macrophages in bronchoalveolar lavage fluid (BALF) and lung parenchyma from lung lysates

respiratory system

increased lung endothelial cell apoptosis ( J:173904 )

• 3 fold increase in caspase 3 activity in lung alveolar cells is measured as early as 4 weeks after doxycycline (dox) induction

abnormal pulmonary acinus morphology ( J:173904 )

• increase in diameters of acinar airspaces (comprising alveolar ducts and alveoli) following dox treatment as compared to controls

dilated pulmonary alveolar duct ( J:173904 )

• following doxycycline induction

overexpanded pulmonary alveolus ( J:173904 )

• following doxycycline induction

emphysema ( J:173904 )

• following doxycycline induction

Genotype
MGI:6275555

cx5

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-TGFA)22.1Kor/0
• Genetic Background: involves: 129 * C57BL/6

growth/size/body

weight loss ( J:101255 )

• mice begin to progressively lose weight after 2 weeks of continuous doxycycline treatment and lose on average 15% of preinduction weight following 6 weeks of doxycycline; females tend to lose more weight than males

homeostasis/metabolism

increased hydroxyproline level ( J:101255 )

• hydroxyproline content in lung is increased over 70% in doxycyline treated mice

respiratory system

abnormal pulmonary acinus morphology ( J:101255 )

• enlarged distal air spaces are detected adjacent to areas of severe adventitial, peribronchial, or pleural fibrosis

pulmonary fibrosis ( J:101255 )

• mice develop progressive pulmonary fibrosis following doxycycline treatment, initially developing in the perivascular adventitia, peribronchial, and pleural regions but later extending into the interstitium

• fibrotic regions are composed of increased collagen, extracellular matrix, and cellular proliferation

• however, inflammatory cell infiltration is not seen in the fibrotic regions

Genotype
MGI:5527337

cx6

• Allelic Composition: Col1a1^{tm1(tetO-EML4/ALK)Kkw}/Col1a1⁺; Tg(Scgb1a1-rtTA)1Jaw/0
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

premature death ( J:166724 )

• doxycycline-treated mice exhibit a median survival of 7 to 8 weeks

neoplasm

abnormal tumor pathology ( J:166724 )

• withdrawal of doxycycline leads to complete tumor regression

• ALK kinase inhibitor is a more effective therapy than chemotherapy in doxycycline-treated mice

increased lung tumor incidence ( J:166724 )

• doxycycline-treated mice develop lung tumorigenesis with a latency of less than 10 days

• however, withdrawal of doxycycline leads to complete tumor regression

increased lung carcinoma incidence ( J:166724 )

• adenocarcinomas predominantly bronchioloalveolar carcinoma with occasional pleural space and airway invasion by an acinar component in doxycycline-treated mice

growth/size/body

weight loss ( J:166724 )

• in tumor-bearing, doxycycline-treated mice in the first 4 weeks

respiratory system

respiratory system phenotype ( J:166724 )

N • untreated mice exhibit normal lung histology

increased lung tumor incidence ( J:166724 )

• doxycycline-treated mice develop lung tumorigenesis with a latency of less than 10 days

• however, withdrawal of doxycycline leads to complete tumor regression

increased lung carcinoma incidence ( J:166724 )

• adenocarcinomas predominantly bronchioloalveolar carcinoma with occasional pleural space and airway invasion by an acinar component in doxycycline-treated mice

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:166724
lung non-small cell carcinoma		DOID:3908		J:166724

Genotype
MGI:5444503

cx7

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-IL1B)KBry/0
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

postnatal lethality, incomplete penetrance ( J:130523 )

• about 50% of newborns from females provided with doxycycline during pregnancy and lactation die before 7 days of age

growth/size/body

decreased body weight ( J:130523 )

• pups from females provided with doxycycline during pregnancy and lactation weight about 36% less than controls

postnatal growth retardation ( J:130523 )

• postnatal growth of newborns from females provided with doxycycline during pregnancy and lactation is decreased

respiratory system

abnormal lung vasculature morphology ( J:130523 )

• pups from females provided with doxycycline during pregnancy and lactation exhibit abnormal vascular development of the lungs, showing capillaries of varying sizes scattered within the thick septa at P3 compared to control lungs that show capillaries lining the alveolar septa, and by P14, capillaries are dysmorphic

lung inflammation ( J:107601 , J:130523 )

• mutants administered doxycycline for 8 days show a 6- to 12-fold increase in the total number of inflammatory cells in bronchoalveolar lavage fluid, mainly due to an influx of neutrophils into the lung; most of the remaining cells are macrophages (J:107601)

• an increase in inflammatory cells is seen in the alveoli and parenchyma of lungs in mutants administered doxycycline for 5 weeks (J:107601)

• however, lung histology is normal in mutants not given doxycycline (J:107601)

• fetal and neonatal lungs in mutants from females provided with doxycycline during pregnancy and lactation exhibit neutrophil and macrophage infiltration in airways and airspaces (J:130523)

• number of neutrophils in the lungs increases rapidly from E18.5 to P0 and remains stable after that time, however the number of macrophages continues to increase during the first week of life (J:130523)

abnormal lung alveolus development ( J:130523 )

• newborns from females provided with doxycycline during pregnancy and lactation exhibit disrupted alveolar development, with absence of septation and thus thicker septa of distal airspaces and an increase in alveolar chord length compared to controls

abnormal lung epithelium morphology ( J:130523 )

• pups from females provided with doxycycline during pregnancy and lactation exhibit thickened epithelium and subepithelial smooth muscle in airway walls, indicating airway remodeling

abnormal pulmonary alveolus morphology ( J:107601 )

• mean alveolar cord length is larger in mutants administered doxycycline for 5 weeks compared to controls

• airway mucus metaplasia in mutants administered doxycycline for 5 weeks

increased pulmonary alveolus wall thickness ( J:130523 )

• newborns from females provided with doxycycline during pregnancy and lactation exhibit increased thickness of saccular/alveolar walls by 23% on P0 and by 38% on P7

overexpanded pulmonary alveolus ( J:107601 )

• severe distal airspace enlargement is seen in mutants administered doxycycline for 5 weeks

thick pulmonary interalveolar septum ( J:130523 )

• newborns from females provided with doxycycline during pregnancy and lactation exhibit thicker septa of distal airspaces

emphysema ( J:107601 )

• mutants administered doxycycline for 5 weeks exhibit distal airspace enlargement consistent with emphysema

abnormal pulmonary elastic fiber morphology ( J:107601 , J:130523 )

• elastin fibers are disrupted, frayed and short in the lungs of mutants administered doxycycline for 5 weeks compared to controls, indicating elastin degradation (J:107601)

• newborns from females provided with doxycycline during pregnancy and lactation exhibit abnormal elastin structure in the distal lung at P7, with poorly organized elastin fibers in the walls of airspaces and lack of elastin in septal crests, and by 3 weeks of age, elastin fibers are splayed and disorganized and are often perpendicular to the airspace wall, have inflammatory cells infiltrating the bundles, and distribution in the blunted secondary crests is abnormal (J:130523)

abnormal bronchiole morphology ( J:107601 )

• bronchiolar thickening and peribronchiolar lymphocytic nodules are seen in mutants administered doxycycline for 5 weeks

pulmonary fibrosis ( J:107601 )

• lung fibrosis with extensive subepithelial fibrosis is seen in mutants administered doxycycline for 5 weeks, with lesions showing increased collagen deposition

increased respiratory mucosa goblet cell number ( J:130523 )

• pups from females provided with doxycycline during pregnancy and lactation exhibit goblet cell hyperplasia

abnormal lung volume ( J:107601 )

• lung volumes and lung volume/body weight ratios are increased after 5 weeks of doxycycline administration

respiratory failure ( J:130523 )

• newborns from females provided with doxycycline during pregnancy and lactation (fetuses receive doxycycline transplacentally and newborns receive it from the mother's milk) develop respiratory insufficiency within several days after birth

immune system

abnormal chemokine level ( J:107601 , J:130523 )

• mutants administered doxycycline for 5 weeks exhibit increased production of CXC chemokines Cxcl1 (KC) and Cxcl2 (MIP-2) (J:107601)

• fetal and neonatal lungs in mutants from females provided with doxycycline during pregnancy and lactation exhibit increased production of chemokines, KC, MIP-2, MCP-1 and MCP-2 (J:130523)

lung inflammation ( J:107601 , J:130523 )

• mutants administered doxycycline for 8 days show a 6- to 12-fold increase in the total number of inflammatory cells in bronchoalveolar lavage fluid, mainly due to an influx of neutrophils into the lung; most of the remaining cells are macrophages (J:107601)

• an increase in inflammatory cells is seen in the alveoli and parenchyma of lungs in mutants administered doxycycline for 5 weeks (J:107601)

• however, lung histology is normal in mutants not given doxycycline (J:107601)

• fetal and neonatal lungs in mutants from females provided with doxycycline during pregnancy and lactation exhibit neutrophil and macrophage infiltration in airways and airspaces (J:130523)

• number of neutrophils in the lungs increases rapidly from E18.5 to P0 and remains stable after that time, however the number of macrophages continues to increase during the first week of life (J:130523)

homeostasis/metabolism

abnormal chemokine level ( J:107601 , J:130523 )

• mutants administered doxycycline for 5 weeks exhibit increased production of CXC chemokines Cxcl1 (KC) and Cxcl2 (MIP-2) (J:107601)

• fetal and neonatal lungs in mutants from females provided with doxycycline during pregnancy and lactation exhibit increased production of chemokines, KC, MIP-2, MCP-1 and MCP-2 (J:130523)

cardiovascular system

abnormal lung vasculature morphology ( J:130523 )

• pups from females provided with doxycycline during pregnancy and lactation exhibit abnormal vascular development of the lungs, showing capillaries of varying sizes scattered within the thick septa at P3 compared to control lungs that show capillaries lining the alveolar septa, and by P14, capillaries are dysmorphic

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
asthma		DOID:2841	OMIM:600807	J:107601
lower respiratory tract disease		DOID:0050161		J:130523

Genotype
MGI:4946282

cx8

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-MYC)36Bop/0
• Genetic Background: involves: 129 * C57BL/6

mortality/aging

premature death ( J:169920 )

• mice fed a diet supplemented with DOX to stimulate transactivating function of the rtTA protein and induce MYC expression exhibit reduced lifespan

neoplasm

increased metastatic potential ( J:169920 )

• 16.7% of DOX treated mice exhibit metastases

increased lung tumor incidence ( J:169920 )

• 100% of tumors show activating Kras mutations

increased lung adenoma incidence ( J:169920 )

• mice treated with DOX develop papillary adenomas

increased lung adenocarcinoma incidence ( J:169920 )

• 23.8% penetrance of adenocarcionomas in untreated mice and 56.7% penetrance in DOX treated mice

respiratory system

increased lung tumor incidence ( J:169920 )

• 100% of tumors show activating Kras mutations

increased lung adenoma incidence ( J:169920 )

• mice treated with DOX develop papillary adenomas

increased lung adenocarcinoma incidence ( J:169920 )

• 23.8% penetrance of adenocarcionomas in untreated mice and 56.7% penetrance in DOX treated mice

Genotype
MGI:5473719

cx9

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-CTGF)#Swu/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J

respiratory system

abnormal lung vasculature morphology ( J:171488 )

• pups nursing on dams administered doxycycline from P1 to P14 exhibit decreased capillary formation in alveolar septa

impaired lung alveolus development ( J:171488 )

• pups nursing on dams administered doxycycline from P1 to P14 exhibit disrupted alveolarization, showing a 27% and 31% decrease in the mean alveolar airspace area and mean cord length, respectively

• pups nursing on dams administered doxycycline from P1 to P14 exhibit disorganized elastic fiber deposition on alveolar surfaces and in septa

abnormal pulmonary interalveolar septum morphology ( J:171488 )

• pups nursing on dams administered doxycycline from P1 to P14 exhibit a 34% decrease in secondary septa

• marker analysis indicates that pups nursing on dams administered doxycycline from P1 to P14 exhibit increased myofibroblast differentiation in alveolar septa

• pups nursing on dams administered doxycycline from P1 to P14 exhibit a 48% increase in the proliferating cell index in alveolar septa

• pups nursing on dams administered doxycycline from P1 to P14 exhibit decreased capillary formation in alveolar septa

pulmonary fibrosis ( J:171488 )

• pups nursing on dams administered doxycycline from P1 to P14 exhibit thickening in the peribronchial/peribronchiolar and perivascular regions of the lungs and increased collagen deposition in these regions, indicating fibrosis

cardiovascular system

abnormal lung vasculature morphology ( J:171488 )

• pups nursing on dams administered doxycycline from P1 to P14 exhibit decreased capillary formation in alveolar septa

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lower respiratory tract disease		DOID:0050161		J:171488

Genotype
MGI:5634289

cx10

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-EGFR*L858R)#Hev/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

neoplasm

increased lung adenocarcinoma incidence ( J:128700 , J:213447 )

• tumor bearing mice treated with the geldanamycin analogue, 17-AAG, which inhibits Hsp90, show a transient degeneration of tumors (J:128700)

• mice treated with doxycycline develop lung adenocarcinomas (J:213447)

• mice treated with doxycycline, followed by treatment with a tyrosine kinase inhibitor erlotinib, initially show tumor regression but eventually develop tumors resistant to long-term erlotinib treatment (J:213447)

• treatment of doxycycline treated mice that have erlotinib-resistant tumors with a MEK inhibitor, trametinib, results in tumor regression (J:213447)

• treatment of doxycline treated mice with trametinib alone does not have an effect on tumor growth (J:213447)

respiratory system

increased lung adenocarcinoma incidence ( J:128700 , J:213447 )

• tumor bearing mice treated with the geldanamycin analogue, 17-AAG, which inhibits Hsp90, show a transient degeneration of tumors (J:128700)

• mice treated with doxycycline develop lung adenocarcinomas (J:213447)

• mice treated with doxycycline, followed by treatment with a tyrosine kinase inhibitor erlotinib, initially show tumor regression but eventually develop tumors resistant to long-term erlotinib treatment (J:213447)

• treatment of doxycycline treated mice that have erlotinib-resistant tumors with a MEK inhibitor, trametinib, results in tumor regression (J:213447)

• treatment of doxycline treated mice with trametinib alone does not have an effect on tumor growth (J:213447)

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:128700 , J:213447

Genotype
MGI:7266256

cx11

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-IGF1R)1Ramo/0
• Genetic Background: involves: 129 * C57BL/6 * FVB

neoplasm

increased lung tumor incidence ( J:271820 )

• mice administered doxycyline beginning at 21 days of age develop tumors on the lung surface as early as 90 days after doxycycline treatment

• most mice treated with doxycycline for up to 9 months exhibit visible lung tumors (2-30 tumors); tumors show multifocal adenomatous alveolar hyperplasia with papillary and solid adenomas

• mice in which doxycycline is removed after an 8-month treatment period show incomplete tumor regression

• however, bronchiolar hyperplasia is not seen in doxycycline treated mice

increased lung adenoma incidence ( J:271820 )

• solid adenomas are seen in doxycycline-treated mice

respiratory system

increased lung tumor incidence ( J:271820 )

• mice administered doxycyline beginning at 21 days of age develop tumors on the lung surface as early as 90 days after doxycycline treatment

• most mice treated with doxycycline for up to 9 months exhibit visible lung tumors (2-30 tumors); tumors show multifocal adenomatous alveolar hyperplasia with papillary and solid adenomas

• mice in which doxycycline is removed after an 8-month treatment period show incomplete tumor regression

• however, bronchiolar hyperplasia is not seen in doxycycline treated mice

increased lung adenoma incidence ( J:271820 )

• solid adenomas are seen in doxycycline-treated mice

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:271820

Genotype
MGI:5781131

cx12

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-EGFR*T790M*L858R)19Kkw/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

immune system

interstitial pneumonia ( J:122849 )

• doxycycline treated mice often exhibit focal pneumonia with increased number of intra-alveolar macrophages filling the alveolar spaces, most likely due to airway obstruction by bronchial tumors

neoplasm

increased metastatic potential ( J:122849 )

• metastatic foci of adenocarcinomas are occasionally seen in lymph nodes of doxycycline treated mice

increased lung tumor incidence ( J:122849 , J:156440 , J:235747 )

• mice develop lung tumors after 5-6 weeks of doxycycline administration (J:122849)

• early lesions develop in alveoli after 2-3 weeks of doxycycline administration (J:122849)

• withdrawal of doxycycline results in decreased proliferation and increased apoptosis of cancer cells and complete tumor regression by 10 days of withdrawal (J:122849)

• mice treated with the WZ4002 compound show an increase in cell apoptosis and decrease in cell proliferation and regression of tumors (J:156440)

• mice treated together with the compound EAI045 (an allosteric tyrosine kinase inhibitor) and cetuximab show regression of tumors, however treatment alone with EAI045 has no effect on tumors (J:235747)

• treatment alone with cetuximab has a minimal effect on tumor regression (J:235747)

increased lung carcinoma incidence ( J:122849 )

• typical bronchioloalveolar carcinoma is seen after 4-5 weeks of doxycycline administration

increased lung adenocarcinoma incidence ( J:122849 )

• invasive peripheral adenocarcinomas with bronchioloalveolar features appears after 7-9 weeks of doxycycline administration and is the dominant histological pattern after 12 weeks of treatment

• early papillary neoplasia in the bronchioles are seen after 2-3 weeks of doxycycline administration which progress into bronchial papillary adenocarcinomas after an additional 6-8 weeks of doxycycline treatment

• both types of lung adenocarcinomas that develop in doxycycline administered mice are resistant to erlotinib treatment

• bronchial tumors that develop in doxycycline administered mice are not sensitive to HKI-272 treatment while peripheral adenocarcinomas show some sensitivity to this treatment

• bronchial and peripheral tumors that develop in doxycycline administered mice are sensitive to combination therapy with HKI-272 and rapamycin

respiratory system

interstitial pneumonia ( J:122849 )

• doxycycline treated mice often exhibit focal pneumonia with increased number of intra-alveolar macrophages filling the alveolar spaces, most likely due to airway obstruction by bronchial tumors

increased lung tumor incidence ( J:122849 , J:156440 , J:235747 )

• mice develop lung tumors after 5-6 weeks of doxycycline administration (J:122849)

• early lesions develop in alveoli after 2-3 weeks of doxycycline administration (J:122849)

• withdrawal of doxycycline results in decreased proliferation and increased apoptosis of cancer cells and complete tumor regression by 10 days of withdrawal (J:122849)

• mice treated with the WZ4002 compound show an increase in cell apoptosis and decrease in cell proliferation and regression of tumors (J:156440)

• mice treated together with the compound EAI045 (an allosteric tyrosine kinase inhibitor) and cetuximab show regression of tumors, however treatment alone with EAI045 has no effect on tumors (J:235747)

• treatment alone with cetuximab has a minimal effect on tumor regression (J:235747)

increased lung carcinoma incidence ( J:122849 )

• typical bronchioloalveolar carcinoma is seen after 4-5 weeks of doxycycline administration

increased lung adenocarcinoma incidence ( J:122849 )

• invasive peripheral adenocarcinomas with bronchioloalveolar features appears after 7-9 weeks of doxycycline administration and is the dominant histological pattern after 12 weeks of treatment

• early papillary neoplasia in the bronchioles are seen after 2-3 weeks of doxycycline administration which progress into bronchial papillary adenocarcinomas after an additional 6-8 weeks of doxycycline treatment

• both types of lung adenocarcinomas that develop in doxycycline administered mice are resistant to erlotinib treatment

• bronchial tumors that develop in doxycycline administered mice are not sensitive to HKI-272 treatment while peripheral adenocarcinomas show some sensitivity to this treatment

• bronchial and peripheral tumors that develop in doxycycline administered mice are sensitive to combination therapy with HKI-272 and rapamycin

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:122849 , J:156440 , J:235747

Genotype
MGI:4410330

cx13

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

Absence of proliferation during goblet cell hyperplasia in Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-Spdef)1Jaw/0 mice

respiratory system

abnormal respiratory mucosa goblet cell morphology ( J:154639 )

• doxycycline-treated mice exhibit goblet cell differentiation without proliferation unlike similarly treated wild-type mice

increased respiratory mucosa goblet cell number ( J:121284 )

• doxycycline-treated mice exhibit hyperplasia of lung goblet cells compared with similarly treated wild-type mice

Genotype
MGI:3834442

cx14

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-PIK3CA*H1047R)13Lca/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

neoplasm

increased lung adenocarcinoma incidence ( J:142254 )

• at 12 weeks following doxycycline treatment, mice develop lung adenocarcinomas

• however, withdrawal of doxycycline or treatment with NVP-BEZ235 leads to tumor regression

respiratory system

increased lung adenocarcinoma incidence ( J:142254 )

• at 12 weeks following doxycycline treatment, mice develop lung adenocarcinomas

• however, withdrawal of doxycycline or treatment with NVP-BEZ235 leads to tumor regression

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:142254

Genotype
MGI:5912341

cx15

• 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:5688300

cx16

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-PTPN11*E76K)#Jiwu/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

neoplasm

increased lung adenoma incidence ( J:212505 )

• atypical adenomatous hyperplasia is seen in mice induced with doxycycline (Dox) for 6 months

• 3 of 12 mice induced with Dox for 6 months develop small lung adenomas

• 13 of 15 mice induced with Dox for 9 months develop lung tumors; tumors at 9 months of Dox induction are larger in size and some progress to adenocarcinoma

• lung tumors regress after Dox withdrawal

increased lung non-small cell carcinoma incidence ( J:212505 )

• lung tumors in Dox treated mice are papillary or mixed subtypes of adenomas and progress to mixed subtypes and solid adenocarcinomas and resemble non-small cell lung cancer

respiratory system

increased lung adenoma incidence ( J:212505 )

• atypical adenomatous hyperplasia is seen in mice induced with doxycycline (Dox) for 6 months

• 3 of 12 mice induced with Dox for 6 months develop small lung adenomas

• 13 of 15 mice induced with Dox for 9 months develop lung tumors; tumors at 9 months of Dox induction are larger in size and some progress to adenocarcinoma

• lung tumors regress after Dox withdrawal

increased lung non-small cell carcinoma incidence ( J:212505 )

• lung tumors in Dox treated mice are papillary or mixed subtypes of adenomas and progress to mixed subtypes and solid adenocarcinomas and resemble non-small cell lung cancer

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:212505

Genotype
MGI:5705252

cx17

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-EGFR*T790M)8Paow/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

neoplasm

increased lung adenocarcinoma incidence ( J:128700 )

• most mice develop lung lesions only after long-term (28-32 weeks) administration of doxycycline (dox)

• lung tumors of dox treated mice are invasive lung adenocarcinomas

• regression of tumors is seen after removal of the inducer dox

• lung tumors of dox treated mice are resistant to treatment with erlotinib

respiratory system

increased lung adenocarcinoma incidence ( J:128700 )

• most mice develop lung lesions only after long-term (28-32 weeks) administration of doxycycline (dox)

• lung tumors of dox treated mice are invasive lung adenocarcinomas

• regression of tumors is seen after removal of the inducer dox

• lung tumors of dox treated mice are resistant to treatment with erlotinib

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:128700

Genotype
MGI:5705253

cx18

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-EGFR*T790M*L858R)51Paow/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/N

respiratory system

increased lung adenocarcinoma incidence ( J:128700 )

• mice on a dox diet for 17.5 weeks of age develop a large lung tumor burden; these are heterogeneous adenocarcinomas involving the solid, bronchioalveolar, and papillary subtypes

• tumors of dox treated mice are negative for CC26, a Clara cell protein, and positive for surfactant protein-C, a type II pneumocyte marker, indicating a type II cell-like phenotype

• regression of tumors is seen as early as one week after removal of the inducer dox, however microscopic islands of tumor cells can still be seen even after mice are off dox for 4 weeks

• lung tumors of dox treated mice are resistant to treatment with erlotinib

• tumor bearing mice treated with the geldanamycin analogue, 17-AAG, which inhibits Hsp90, show tumor necrosis although viable tumor nodules remain

• however, mice maintained without dox exhibit normal lung morphology

tachypnea ( J:128700 )

• mice on a doxycycline (dox)-containing diet for 17.5 weeks become tachypneic

neoplasm

increased lung adenocarcinoma incidence ( J:128700 )

• mice on a dox diet for 17.5 weeks of age develop a large lung tumor burden; these are heterogeneous adenocarcinomas involving the solid, bronchioalveolar, and papillary subtypes

• tumors of dox treated mice are negative for CC26, a Clara cell protein, and positive for surfactant protein-C, a type II pneumocyte marker, indicating a type II cell-like phenotype

• regression of tumors is seen as early as one week after removal of the inducer dox, however microscopic islands of tumor cells can still be seen even after mice are off dox for 4 weeks

• lung tumors of dox treated mice are resistant to treatment with erlotinib

• tumor bearing mice treated with the geldanamycin analogue, 17-AAG, which inhibits Hsp90, show tumor necrosis although viable tumor nodules remain

• however, mice maintained without dox exhibit normal lung morphology

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:128700

Genotype
MGI:6256808

cx19

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

neoplasm

increased lung tumor incidence ( J:156440 , J:235747 )

• doxycycline treated mice develop lung cancer (J:156440)

• mice treated with the WZ4002 compound show an increase in cell apoptosis and decrease in cell proliferation and regression of tumors (J:156440)

• treatment together with the compound EAI045 (an allosteric tyrosine kinase inhibitor) and cetuximab has no effect on tumor growth (J:235747)

respiratory system

increased lung tumor incidence ( J:156440 , J:235747 )

• doxycycline treated mice develop lung cancer (J:156440)

• mice treated with the WZ4002 compound show an increase in cell apoptosis and decrease in cell proliferation and regression of tumors (J:156440)

• treatment together with the compound EAI045 (an allosteric tyrosine kinase inhibitor) and cetuximab has no effect on tumor growth (J:235747)

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:156440 , J:235747

Genotype
MGI:6275557

cx20

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-TGFA)22.1Kor/0
• Genetic Background: involves: 129 * C57BL/6 * FVB/NJ

homeostasis/metabolism

increased hydroxyproline level ( J:240947 )

• hydroxyproline content is increased in the lungs of doxycycline treated mice

respiratory system

pulmonary fibrosis ( J:240947 )

• mice develop progressive pulmonary fibrosis in in the pleural and perivascular adventitia regions following doxycycline treatment

• however, 4 weeks after ending doxycycline treatment, fibrosis partially resolves

pulmonary interstitial fibrosis ( J:240947 )

• doxycycline treated mice show fibrosis extending from the subpleural and adventitial regions into the interstitium; these lesions grow in both number and volume throughout 7 weeks of doxycycline treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pulmonary fibrosis		DOID:3770		J:240947

Genotype
MGI:5912294

cx21

• 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

cx22

• 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:3690090

cx23

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-EGFR*L858R)57Hev/0
• Genetic Background: involves: C57BL/6 * CBA

respiratory system

increased lung adenocarcinoma incidence ( J:109092 )

• as early as 2 weeks after initiation of doxycycline, lungs of bitransgenic mice exhibit scattered thickening of the alveolar walls due to proliferation of abnormal pneumocytes, with a lepidic growth pattern similar to human bronchioalveolar carcinoma (BAC), a subtype of lung adenocarcinoma; this wall thickening may be progressive, gradually compressing the air spaces

• after longer than 4 weeks on doxycycline, bitransgenic mice develop multifocal invasive adenocarcinoma of the lungs, with papilliform tumors of varying size embedded in the abnormal lung parenchyma; the adenocarcinoma cells have moderately pleomorphic nuclei with large nucleoli

• immunohistochemical analysis demonstrates that the tumors in these mice express the mutant human EGFR protein and that they are composed of cells that express surfactant protein C, characteristic of type II pneumocytes, but not Clara cell protein CC26

• discontinuation of doxycycline treatment in two mice after 43 and 55 days resulted in complete disappearance of lung opacities on MRI within a week; histologic examination at 32 and 169 days after deinduction revealed that the tumors had regressed completely, in one case leaving scar tissue

• treatment of tumor-bearing mice with the tyrosine kinase inhibitor erlotinib, while the mice continued receiving doxycycline, resulted in partial to complete disappearance of opacities on MRI in 2-8 days and, in mice examined after at least 4 days on erlotinib, complete or nearly complete (i.e., some residual tumor cells remained) histological regression of the tumors

abnormal type II pneumocyte morphology ( J:109092 )

• after only 4 days' induction with doxycycline, lung tissue from doubly transgenic mice contained nearly 2-fold the number of type II pneumocytes, identified by staining with antibody against surfactant protein C, than control tissue

• immunohistochemical analysis demonstrates that the tumors induced by doxycycline in these mice express the mutant human EGFR protein and that they are composed of cells that express surfactant protein C, characteristic of type II pneumocytes, but not Clara cell protein CC26

thick pulmonary interalveolar septum ( J:109092 )

neoplasm

increased lung adenocarcinoma incidence ( J:109092 )

• as early as 2 weeks after initiation of doxycycline, lungs of bitransgenic mice exhibit scattered thickening of the alveolar walls due to proliferation of abnormal pneumocytes, with a lepidic growth pattern similar to human bronchioalveolar carcinoma (BAC), a subtype of lung adenocarcinoma; this wall thickening may be progressive, gradually compressing the air spaces

• after longer than 4 weeks on doxycycline, bitransgenic mice develop multifocal invasive adenocarcinoma of the lungs, with papilliform tumors of varying size embedded in the abnormal lung parenchyma; the adenocarcinoma cells have moderately pleomorphic nuclei with large nucleoli

• immunohistochemical analysis demonstrates that the tumors in these mice express the mutant human EGFR protein and that they are composed of cells that express surfactant protein C, characteristic of type II pneumocytes, but not Clara cell protein CC26

• discontinuation of doxycycline treatment in two mice after 43 and 55 days resulted in complete disappearance of lung opacities on MRI within a week; histologic examination at 32 and 169 days after deinduction revealed that the tumors had regressed completely, in one case leaving scar tissue

• treatment of tumor-bearing mice with the tyrosine kinase inhibitor erlotinib, while the mice continued receiving doxycycline, resulted in partial to complete disappearance of opacities on MRI in 2-8 days and, in mice examined after at least 4 days on erlotinib, complete or nearly complete (i.e., some residual tumor cells remained) histological regression of the tumors

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:109092

Genotype
MGI:3690458

cx24

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-EGFR*delta19)11Hev/0
• Genetic Background: involves: C57BL/6 * CBA

respiratory system

increased lung adenocarcinoma incidence ( J:109092 )

• a bitransgenic mouse examined after 13 days on doxycycline exhibited scattered thickening of the alveolar walls due to proliferation of abnormal pneumocytes, with a lepidic growth pattern similar to human bronchioalveolar carcinoma (BAC); animals examined after 28 days or longer on doxycycline exhibited BAC-like lesions at the lung periphery

• mice on doxycycline 28 days or longer exhibit multifocal, frondiform tumors radiating from bronchioalveolar duct junctions (BADJ) into the surrounding, BAC-free parenchyma; more advanced tumors form compact papilliform masses

• discontinuation of doxycycline treatment in two mice after 99 and 168 days resulted in partial remission of lung opacities on MRI at 6 and 4 days, respectively; histologic examination 4 days after deinduction found tumors still present, but at 31 days revealed that the tumors had regressed completely, leaving scar tissue

• treatment of two tumor-bearing bitransgenic mice (the second heterozygous for a Trp53-inactivating mutation) with the tyrosine kinase inhibitor erlotinib, while the mice continued receiving doxycycline, resulted in partial disappearance of opacities on MRI at 4 and 14 days and, after 4 days and 4 weeks on erlotinib, respectively, nearly complete histological regression of the tumors (i.e., some residual tumor cells remained)

abnormal pulmonary alveolus epithelial cell morphology ( J:109092 )

• a bitransgenic mouse examined histologically 8 days after initiation of doxycycline exhibited proliferative lung lesions characteristic of early atypical adenomatous hyperplasia (AHH) at the lung periphery

abnormal type II pneumocyte morphology ( J:109092 )

• immunohistochemical analysis demonstrates that the tumors induced in these mice express the mutant human EGFR protein and that they are composed of cells that express surfactant protein C, characteristic of type II pneumocytes, but not Clara cell protein CC26

abnormal bronchoalveolar duct junction morphology ( J:109092 )

• bitransgenic mice on doxycycline 28 days or longer exhibit multifocal, frondiform tumors arising and radiating from bronchioalveolar duct junctions (BADJ) into the surrounding, BAC-free parenchyma; more advanced tumors form compact papilliform masses

neoplasm

increased lung adenocarcinoma incidence ( J:109092 )

• a bitransgenic mouse examined after 13 days on doxycycline exhibited scattered thickening of the alveolar walls due to proliferation of abnormal pneumocytes, with a lepidic growth pattern similar to human bronchioalveolar carcinoma (BAC); animals examined after 28 days or longer on doxycycline exhibited BAC-like lesions at the lung periphery

• mice on doxycycline 28 days or longer exhibit multifocal, frondiform tumors radiating from bronchioalveolar duct junctions (BADJ) into the surrounding, BAC-free parenchyma; more advanced tumors form compact papilliform masses

• discontinuation of doxycycline treatment in two mice after 99 and 168 days resulted in partial remission of lung opacities on MRI at 6 and 4 days, respectively; histologic examination 4 days after deinduction found tumors still present, but at 31 days revealed that the tumors had regressed completely, leaving scar tissue

• treatment of two tumor-bearing bitransgenic mice (the second heterozygous for a Trp53-inactivating mutation) with the tyrosine kinase inhibitor erlotinib, while the mice continued receiving doxycycline, resulted in partial disappearance of opacities on MRI at 4 and 14 days and, after 4 days and 4 weeks on erlotinib, respectively, nearly complete histological regression of the tumors (i.e., some residual tumor cells remained)

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:109092

Genotype
MGI:3690087

cx25

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-EGFR*L858R)56Hev/0
• Genetic Background: involves: C57BL/6 * CBA

respiratory system

increased lung adenocarcinoma incidence ( J:109092 )

• as early as 2 weeks after initiation of doxycycline, lungs of bitransgenic mice exhibit scattered thickening of the alveolar walls due to proliferation of abnormal pneumocytes, with a lepidic growth pattern similar to human bronchioalveolar carcinoma (BAC), a subtype of lung adenocarcinoma; this wall thickening may be progressive, gradually compressing the air spaces

• after longer than 4 weeks on doxycycline, bitransgenic mice develop multifocal invasive adenocarcinoma of the lungs, with papilliform tumors of varying size embedded in the abnormal lung parenchyma; the adenocarcinoma cells have moderately pleomorphic nuclei with large nucleoli

• immunohistochemical analysis demonstrates that the tumors in these mice express the mutant human EGFR protein and that they are composed of cells that express surfactant protein C, characteristic of type II pneumocytes, but not Clara cell protein CC26

• discontinuation of doxycycline treatment in two mice after 122 and 180 days resulted in diminution of lung opacities on MRI at 9 and 2 days afterward; histologic examination of the second mouse immediately after MRI found tumors present, whereas examination of the first mouse 31 days after deinduction revealed that the tumors had regressed completely, leaving scar tissue

• treatment of tumor-bearing mice with the tyrosine kinase inhibitor erlotinib, while the mice continued receiving doxycycline, resulted in partial to complete disappearance of opacities on MRI in all mice on at least 12.5 mg kg^-1 d^-1 erlotinib and, in mice examined after at least 4 days on erlotinib, complete or nearly complete (i.e., some residual tumor cells remained) histological regression of the tumors

abnormal type II pneumocyte morphology ( J:109092 )

• after only 4 days' induction with doxycycline, lung tissue from doubly transgenic mice contained nearly 2-fold the number of type II pneumocytes, identified by staining with antibody against surfactant protein C, than control tissue

• immunohistochemical analysis demonstrates that the tumors induced by doxycycline in these mice express the mutant human EGFR protein and that they are composed of cells that express surfactant protein C, characteristic of type II pneumocytes, but not Clara cell protein CC26

thick pulmonary interalveolar septum ( J:109092 )

• as early as 2 weeks after initiation of doxycycline, lungs of bitransgenic mice exhibit scattered thickening of the alveolar walls due to proliferation of abnormal pneumocytes, with a lepidic growth pattern similar to human bronchioalveolar carcinoma (BAC), a subtype of lung adenocarcinoma; this wall thickening may be progressive, gradually compressing the air spaces

neoplasm

increased lung adenocarcinoma incidence ( J:109092 )

• as early as 2 weeks after initiation of doxycycline, lungs of bitransgenic mice exhibit scattered thickening of the alveolar walls due to proliferation of abnormal pneumocytes, with a lepidic growth pattern similar to human bronchioalveolar carcinoma (BAC), a subtype of lung adenocarcinoma; this wall thickening may be progressive, gradually compressing the air spaces

• after longer than 4 weeks on doxycycline, bitransgenic mice develop multifocal invasive adenocarcinoma of the lungs, with papilliform tumors of varying size embedded in the abnormal lung parenchyma; the adenocarcinoma cells have moderately pleomorphic nuclei with large nucleoli

• immunohistochemical analysis demonstrates that the tumors in these mice express the mutant human EGFR protein and that they are composed of cells that express surfactant protein C, characteristic of type II pneumocytes, but not Clara cell protein CC26

• discontinuation of doxycycline treatment in two mice after 122 and 180 days resulted in diminution of lung opacities on MRI at 9 and 2 days afterward; histologic examination of the second mouse immediately after MRI found tumors present, whereas examination of the first mouse 31 days after deinduction revealed that the tumors had regressed completely, leaving scar tissue

• treatment of tumor-bearing mice with the tyrosine kinase inhibitor erlotinib, while the mice continued receiving doxycycline, resulted in partial to complete disappearance of opacities on MRI in all mice on at least 12.5 mg kg^-1 d^-1 erlotinib and, in mice examined after at least 4 days on erlotinib, complete or nearly complete (i.e., some residual tumor cells remained) histological regression of the tumors

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:109092

Genotype
MGI:2652187

cx26

• Allelic Composition: Tg(tetO-Plau)1Ths/0; Tg(Scgb1a1-rtTA)1Jaw/0
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:80184 )

• mice exhibit decreased mortality rate following bleomycin-induced lung injury

homeostasis/metabolism

decreased susceptibility to xenobiotic induced morbidity/mortality ( J:80184 )

• mice exhibit decreased mortality rate following bleomycin-induced lung injury

Genotype
MGI:5912489

cx27

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-ERBB2*)5BKkw/0
• Genetic Background: involves: FVB/N

mortality/aging

premature death ( J:143874 )

• caused by asphyxiation due to intrabronchial carcinoma in doxycycline-treated mice

• all doxycycline-treated mice die by 30 weeks

neoplasm

increased lung tumor incidence ( J:143874 )

• in doxycycline-treated mice after 2 to 3 weeks with increasing tumor volume over a 30 week period

• tumors in doxycycline-treated mice develop from bronchiolar epithelium

• however, withdrawal of doxycycline leads to tumor regression

increased lung carcinoma incidence ( J:143874 )

• intrabronchal carcinomas after 15 to 18 weeks leading to asphyxiation in doxycycline-treated mice

increased lung non-small cell carcinoma incidence ( J:143874 )

• doxycycline-treated mice develop adenosquamous carcinomas

respiratory system

increased lung tumor incidence ( J:143874 )

• in doxycycline-treated mice after 2 to 3 weeks with increasing tumor volume over a 30 week period

• tumors in doxycycline-treated mice develop from bronchiolar epithelium

• however, withdrawal of doxycycline leads to tumor regression

increased lung carcinoma incidence ( J:143874 )

• intrabronchal carcinomas after 15 to 18 weeks leading to asphyxiation in doxycycline-treated mice

increased lung non-small cell carcinoma incidence ( J:143874 )

• doxycycline-treated mice develop adenosquamous carcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adenosquamous lung carcinoma		DOID:4829		J:143874

Genotype
MGI:5912488

cx28

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO-ERBB2*)26Kkw/0
• Genetic Background: involves: FVB/N

mortality/aging

premature death ( J:143874 )

• caused by asphyxiation due to intrabronchial carcinoma in doxycycline-treated mice

• all doxycycline-treated mice die by around 10 weeks

neoplasm

increased lung tumor incidence ( J:143874 )

• in doxycycline-treated mice after 1 week with increasing tumor volume over an 8 week period

• tumors in doxycycline-treated mice develop from bronchiolar epithelium

• however, withdrawal of doxycycline leads to tumor regression

increased lung carcinoma incidence ( J:143874 )

• intrabronchal carcinomas after 3 to 4 weeks leading to asphyxiation in doxycycline-treated mice

increased lung non-small cell carcinoma incidence ( J:143874 )

• doxycycline-treated mice develop adenosquamous carcinomas

respiratory system

increased lung tumor incidence ( J:143874 )

• in doxycycline-treated mice after 1 week with increasing tumor volume over an 8 week period

• tumors in doxycycline-treated mice develop from bronchiolar epithelium

• however, withdrawal of doxycycline leads to tumor regression

increased lung carcinoma incidence ( J:143874 )

• intrabronchal carcinomas after 3 to 4 weeks leading to asphyxiation in doxycycline-treated mice

increased lung non-small cell carcinoma incidence ( J:143874 )

• doxycycline-treated mice develop adenosquamous carcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adenosquamous lung carcinoma		DOID:4829		J:143874

Genotype
MGI:3586366

cx29

• Allelic Composition: Tg(tetO-Vegfa)90Ala/?; Tg(Scgb1a1-rtTA)1Jaw/?
• Genetic Background: involves: FVB/N

respiratory system

abnormal lung development ( J:86840 )

• administration of doxycycline to pregnant mother and consequent VEGF-A164 expression in conducting airway epithelial cells of E10.5 to E16.5 embryo caused irregular evagination of epithelium into the lumen of bronchi and bronchioli

Genotype
MGI:3693292

cx30

• Allelic Composition: Tg(Scgb1a1-rtTA)1Jaw/0; Tg(tetO/CMV-KRAS*G12C)9.1Msmi/0
• Genetic Background: involves: FVB/N

respiratory system

abnormal lung morphology ( J:102839 )

• after 12 days of doxycycline (DOX) treatement, small, hyperplastic lung foci are detected; untreated mice have normal lungs

increased lung adenoma incidence ( J:102839 )

• single adenoma was detected at 3 months; at 6, 9, and 12 months of treatment, incidence increases; mice develop higher incidence of proliferative changes with lower latency than SFTPC/KRAS mice

increased lung adenocarcinoma incidence ( J:102839 )

• at 12 months of treatment, 2 adenomas have progressed to low grade carcinomas

abnormal pulmonary alveolus epithelium morphology ( J:102839 )

• after 5 weeks of DOX treatment, extensive epithelial hyperplasia of alveolar region of lung is observed; untreated mice have normal lungs

neoplasm

increased tumor incidence ( J:102839 )

• after 3 months treatment, visible macroscopic lesions are found; tumor incidence at 3 months is 55%, with multiplicity of 3.5 tumors/mouse

• lesions are <1mm in size

• early hyperplastic lesions are of bronchiolar origin

• at 6 and 9 months DOX treatment, visible lesions increase in number; multiplicity is 28.8 and 34 tumors/mouse after 9 and 12 months, higher than SFTPC/KRAS bitransgenic mice; treated monotransgenic mice show no tumor incidence

• when DOX treatment was stopped after 9 months, within 2 weeks only 4 tumors are visible on lung surface; these remain after 1 months; minimal hyperplastic foci microscopically are detectable, showing no proliferation (or apoptosis)

increased lung adenoma incidence ( J:102839 )

• single adenoma was detected at 3 months; at 6, 9, and 12 months of treatment, incidence increases; mice develop higher incidence of proliferative changes with lower latency than SFTPC/KRAS mice

increased lung adenocarcinoma incidence ( J:102839 )

• at 12 months of treatment, 2 adenomas have progressed to low grade carcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lung benign neoplasm		DOID:3683		J:102839