Tg(Scgb1a1-rtTA)1Jaw Transgene Detail MGI Mouse (MGI:2445707)

Tg(Scgb1a1-rtTA)1Jaw
Transgene Detail

Nomenclature

Symbol:	Tg(Scgb1a1-rtTA)1Jaw
Name:	transgene insertion 1, Jeffrey A Whitsett
MGI ID:	MGI:2445707
Synonyms:	CC10-rtTA, CCSP-rtTA, CCSP^tg, Tg(Ugb-rtTA)1Jaw
Transgene:	Tg(Scgb1a1-rtTA)1Jaw Location: unknown

Transgene
origin

Strain of Origin:

129 and C57BL/6

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	The transgene is composed of 2.3 kb of rat Ugb (Scgb1a1) promoter, a reverse tetracycline responsive transactivator gene (rt-TA), and 2 kb of human growth hormone sequences, which includes introns and a polyadenylation signal. Transgene expression was confirmed by RT-PCR analysis. The rat Scgb1a1 promoter is active in respiratory epithelial cells. (J:61736)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:

Mouse Strains: 3 strains available Cell Lines: 0 lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	cn1	tg2	tg3	tg4	tg5	tg6	tg7	tg8
homeostasis/metabolism							√
decreased sensitivity to xenobiotic induced morbidity/mortality							√
		cn1	tg2	tg3	tg4	tg5	tg6	tg7	tg8
immune system		N
immune system phenotype		N
		cn1	tg2	tg3	tg4	tg5	tg6	tg7	tg8
life span/aging							√
decreased sensitivity to xenobiotic induced morbidity/mortality							√
		cn1	tg2	tg3	tg4	tg5	tg6	tg7	tg8
respiratory system		√		√	√	√		√	√
abnormal respiratory mucosa goblet cell morphology		√
abnormal respiratory mechanics		√
abnormal airway resistance		√
abnormal lung compliance		√
abnormal lung development								√
abnormal lung morphology									√
thick alveolar septum				√	√
abnormal respiratory alveolar epithelial cell morphology						√			√
abnormal type II pneumocyte morphology				√	√	√
abnormal bronchoalveolar duct junctions						√
		cn1	tg2	tg3	tg4	tg5	tg6	tg7	tg8
tumorigenesis			√	√	√	√			√
increased tumor incidence									√
lung adenocarcinoma			√	√	√	√			√
lung adenoma									√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
cn1	Foxa2^tm1Khk/Foxa2^tm1Khk Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-cre)1Jaw/0	Not Specified
immune system immune system phenotype (J:88601) no increase in the number of neutrophils or macrophages in mice treated with doxycycline from E0 through P16 respiratory system abnormal respiratory mucosa goblet cell morphology (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) abnormal airway resistance (J:88601) increased in mice treated with doxycycline abnormal lung compliance (J:88601) decreased in mice treated with doxycycline
Genotype	Allelic Composition	Genetic Background
tg2	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-PIK3CA*H1047R)13Lca/0	involves: 129 * C57BL/6 * FVB/N
tumorigenesis lung adenocarcinoma (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
Genotype	Allelic Composition	Genetic Background
tg3	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*L858R)56Hev/0	involves: C57BL/6 * CBA
respiratory system 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 alveolar 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 tumorigenesis lung adenocarcinoma (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
Genotype	Allelic Composition	Genetic Background
tg4	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*L858R)57Hev/0	involves: C57BL/6 * CBA
respiratory system 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 alveolar septum (J:109092) tumorigenesis lung adenocarcinoma (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
Genotype	Allelic Composition	Genetic Background
tg5	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO-EGFR*delta19)11Hev/0	involves: C57BL/6 * CBA
respiratory system abnormal respiratory alveolar 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 junctions (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 tumorigenesis lung adenocarcinoma (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)
Genotype	Allelic Composition	Genetic Background
tg6	Tg(tetO-Plau)1Ths/0 Tg(Scgb1a1-rtTA)1Jaw/0	involves: C57BL/6 * SJL
life span/aging decreased sensitivity to xenobiotic induced morbidity/mortality (J:80184) mice exhibit decreased mortality rate following bleomycin-induced lung injury homeostasis/metabolism decreased sensitivity to xenobiotic induced morbidity/mortality (J:80184) mice exhibit decreased mortality rate following bleomycin-induced lung injury
Genotype	Allelic Composition	Genetic Background
tg7	Tg(tetO-Vegfa)90Ala/? Tg(Scgb1a1-rtTA)1Jaw/?	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	Allelic Composition	Genetic Background
tg8	Tg(Scgb1a1-rtTA)1Jaw/0 Tg(tetO/CMV-KRAS*G12C)9.1Msmi/0	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 abnormal respiratory alveolar epithelial cell morphology (J:102839) after 5 weeks of DOX treatment, extensive epithelial hyperplasia of alveolar region of lung is observed; untreated mice have normal lungs tumorigenesis 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) lung adenoma (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 lung adenocarcinoma (J:102839) at 12 months of treatment, 2 adenomas have progressed to low grade carcinomas

References

Original:	J:61736 Tichelaar JW et al., "Conditional expression of fibroblast growth factor-7 in the developing and mature lung." J Biol Chem 2000 Apr 21;275(16):11858-64
All:	54 reference(s)

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