Phenotypes associated with this allele

• Allele Symbol: Scgb1a1^{tm1.1(cre)Fjd}
• Allele Name: targeted mutation 1.1, Franco J DeMayo
• Allele ID: MGI:3797250
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pten^tm1Hwu/Pten^tm1Hwu Scgb1a1^tm1.1(cre)Fjd/Scgb1a1^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4839214
cn2	Kras^tm4Tyj/Kras^+ Scgb1a1^tm1.1(cre)Fjd/Scgb1a1^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4839215
cn3	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^tm1Hwu Scgb1a1^tm1.1(cre)Fjd/Scgb1a1^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4839216
cn4	Kras^tm4Tyj/Kras^+ Scgb1a1^tm1.1(cre)Fjd/Scgb1a1^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:8226385
ot5	Scgb1a1^tm1.1(cre)Fjd/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3805839

Genotype
MGI:4839214

cn1

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Scgb1a1^{tm1.1(cre)Fjd}/Scgb1a1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

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

normal phenotype

no abnormal phenotype detected ( J:131721 )

• mice are viable and exhibit not visible abnormalities and remain healthy throughout 12 months of study, with normal lungs

Genotype
MGI:4839215

cn2

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Scgb1a1^{tm1.1(cre)Fjd}/Scgb1a1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

premature death ( J:131721 )

• average survival is 24 weeks

respiratory system

abnormal lung morphology ( J:131721 )

• mutants develop lung lesions that are first detected at 12 weeks of age in alveoli and bronchioles

• mutants develop epithelial lesions termed atypical papillary bronchiolar proliferation that has papillary proliferations of the bronchiolar epithelium located at the bronchiolar terminal site

• however, no carcinomas are seen by 24 weeks of age

increased lung tumor incidence ( J:131721 )

• mutants develop lung lesions that are first detected at 12 weeks of age in alveoli and bronchioles

• mutants develop epithelial lesions termed atypical papillary bronchiolar proliferation that has papillary proliferations of the bronchiolar epithelium located at the bronchiolar terminal site

increased lung adenoma incidence ( J:131721 )

• atypical adenomatous hyperplasia lesions and adenomas

neoplasm

increased lung tumor incidence ( J:131721 )

• mutants develop lung lesions that are first detected at 12 weeks of age in alveoli and bronchioles

• mutants develop epithelial lesions termed atypical papillary bronchiolar proliferation that has papillary proliferations of the bronchiolar epithelium located at the bronchiolar terminal site

increased lung adenoma incidence ( J:131721 )

• atypical adenomatous hyperplasia lesions and adenomas

Genotype
MGI:4839216

cn3

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten^tm1Hwu; Scgb1a1^{tm1.1(cre)Fjd}/Scgb1a1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

premature death ( J:131721 )

• mean survival is 8 weeks

immune system

lung inflammation ( J:131721 )

• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression

respiratory system

lung inflammation ( J:131721 )

• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression

increased lung tumor incidence ( J:131721 )

• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants

• mutants develop distinct bronchial and alveolar tumors

increased lung adenoma incidence ( J:131721 )

• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions

increased lung carcinoma incidence ( J:131721 )

• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation

increased lung adenocarcinoma incidence ( J:131721 )

• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma

tachypnea ( J:131721 )

• by 2 months of age, mutants exhibit tachypnea

neoplasm

increased lung tumor incidence ( J:131721 )

• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants

• mutants develop distinct bronchial and alveolar tumors

increased lung adenoma incidence ( J:131721 )

• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions

increased lung carcinoma incidence ( J:131721 )

• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation

increased lung adenocarcinoma incidence ( J:131721 )

• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma

growth/size/body

weight loss ( J:131721 )

• by 2 months of age, mutants exhibit weight loss

Genotype
MGI:8226385

cn4

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Scgb1a1^{tm1.1(cre)Fjd}/Scgb1a1⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

mortality/aging

premature death ( J:159271 )

• shortened life span, with a median survival time of 6 months and no mice surviving past 8 months of age

decreased tumor-free survival time ( J:159271 )

• shortened life span due to lung tumors

neoplasm

increased tumor growth/size ( J:159271 )

• weekly exposure to aerosolized nontypeable Haemophilus influenzae lystate (NTHi) for 8 weeks to induce chronic obstructive pulmonary disease (COPD)-like chronic airway inflammation increases lung surface tumors 3.2-fold while no tumors are seen in NTHi treated wild-type mice

increased lung tumor incidence ( J:159271 )

• isolated small lesions in the lungs are seen in 1- and 2-month-old mice and an increase in lesion size is seen with age

• however, no lesions are seen in other organs, including brain, liver, kidney, intestine, and muscle and no metastases are seen

• lesions are atypical papillary bronchiolar hyperplasia, solid and papillary adenomas, adenomas with atypical cytologic features, atypical papillary bronchiolar hyperplasia adjacent to adenomas, and adenoncarcinoma

• the main lesions are epithelial hyperplasia in the early stage and adenomas in the middle and late stages

• early lung lesions exhibit a Clara cell phenotype indicating that lesions come from Clara Cells of conducting airways and more advanced pathologies show an alveolar type II cell phenotype

• weekly exposure to aerosolized nontypable Haemophilus influenzae lysate results in an increase in total lung tumor burden

increased lung adenoma incidence ( J:159271 )

• lesions include solid and papillary adenomas and adenomas with atypical cytologic features

• adenomas are predominately of the papillary subtype

• number of adenomas is greater than in Kras^tm4Tyj Scgb1a1^tm1(cre)Fjd mice but the mean size of adenomas is smaller

increased lung adenocarcinoma incidence ( J:159271 )

respiratory system

lung inflammation ( J:159271 )

• mice show elevated macrophage numbers in bronchoalveolar lavage fluid (BALF)

• 14-week-old mice show focal infiltration of macrophages around hyperplastic and adenomatous lesions

• focal to extensive acidophilic pneumonia is seen surrounding adenomas and adenocarcinomas in 30% of the total lung tumors

• mice exposed to aerosolized nontypeable Haemophilus influenzae lystate (NTHi) once weekly for 8 weeks to induce chronic obstructive pulmonary disease (COPD)-like chronic airway inflammation show dense infiltration of the lung parenchyma with macrophages, neutrophils, and lymphocytes indicating neutrophil/macrophage/CD8 T cell-associated COPD-like airway inflammation; the inflammatory infiltrate is centered around airways and blood vessels, but also extends widely into alveolar spaces

increased lung tumor incidence ( J:159271 )

• isolated small lesions in the lungs are seen in 1- and 2-month-old mice and an increase in lesion size is seen with age

• however, no lesions are seen in other organs, including brain, liver, kidney, intestine, and muscle and no metastases are seen

• lesions are atypical papillary bronchiolar hyperplasia, solid and papillary adenomas, adenomas with atypical cytologic features, atypical papillary bronchiolar hyperplasia adjacent to adenomas, and adenoncarcinoma

• the main lesions are epithelial hyperplasia in the early stage and adenomas in the middle and late stages

• early lung lesions exhibit a Clara cell phenotype indicating that lesions come from Clara Cells of conducting airways and more advanced pathologies show an alveolar type II cell phenotype

• weekly exposure to aerosolized nontypable Haemophilus influenzae lysate results in an increase in total lung tumor burden

increased lung adenoma incidence ( J:159271 )

• lesions include solid and papillary adenomas and adenomas with atypical cytologic features

• adenomas are predominately of the papillary subtype

• number of adenomas is greater than in Kras^tm4Tyj Scgb1a1^tm1(cre)Fjd mice but the mean size of adenomas is smaller

increased lung adenocarcinoma incidence ( J:159271 )

bronchiolar epithelial hyperplasia ( J:159271 )

• in early stages, epithelial hyperplasia is only seen in bronchioles, not in the alveolar sac area

• lesions include atypical papillary bronchiolar hyperplasia and atypical papillary bronchiolar hyperplasia adjacent to adenomas

immune system

lung inflammation ( J:159271 )

• mice show elevated macrophage numbers in bronchoalveolar lavage fluid (BALF)

• 14-week-old mice show focal infiltration of macrophages around hyperplastic and adenomatous lesions

• focal to extensive acidophilic pneumonia is seen surrounding adenomas and adenocarcinomas in 30% of the total lung tumors

• mice exposed to aerosolized nontypeable Haemophilus influenzae lystate (NTHi) once weekly for 8 weeks to induce chronic obstructive pulmonary disease (COPD)-like chronic airway inflammation show dense infiltration of the lung parenchyma with macrophages, neutrophils, and lymphocytes indicating neutrophil/macrophage/CD8 T cell-associated COPD-like airway inflammation; the inflammatory infiltrate is centered around airways and blood vessels, but also extends widely into alveolar spaces

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:159271

Genotype
MGI:3805839

ot5

• Allelic Composition: Scgb1a1^{tm1.1(cre)Fjd}/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:136676 )

• mice are viable and fertile with normal lung morphology