Phenotypes associated with this allele

• Allele Symbol: Tg(tetO-cre)3Jig
• Allele Name: transgene insertion 3, Jeffrey I Gordon
• Allele ID: MGI:3041443
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Kras^tm1Bbd/Kras^+ Trp53^tm1Brd/Trp53^+ Tg(Cela1-tTA)#Eps/? Tg(tetO-cre)3Jig/?	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * FVB/N	MGI:5502432
cn2	Clcn3^tm1.1Jrhm/Clcn3^tm1.1Jrhm Tg(Myh6-tTA)6Smbf/0 Tg(tetO-cre)3Jig/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:5706585
cn3	Kras^tm1Bbd/Kras^tm1Bbd Tg(Cela1-tTA)#Eps/? Tg(tetO-cre)3Jig/?	involves: 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5502430

Genotype
MGI:5502432

cn1

• Allelic Composition: Kras^tm1Bbd/Kras⁺; Trp53^tm1Brd/Trp53⁺; Tg(Cela1-tTA)#Eps/?; Tg(tetO-cre)3Jig/?
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * FVB/N

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

mortality/aging

premature death ( J:119988 )

• 50% mortality by 6 months of age

• 100% mortality by 1 year of age

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:119988 )

• all mice develop moderately to poorly differentiated pancreatic ductal adenocarcinomas, peritoneal explants, and perineural extensions

increased metastatic potential ( J:119988 )

• metastases develop affecting liver, diaphragm, lungs, lymph nodes, and spleen

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:119988 )

• all mice develop moderately to poorly differentiated pancreatic ductal adenocarcinomas, peritoneal explants, and perineural extensions

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:119988

Genotype
MGI:5706585

cn2

• Allelic Composition: Clcn3^tm1.1Jrhm/Clcn3^tm1.1Jrhm; Tg(Myh6-tTA)6Smbf/0; Tg(tetO-cre)3Jig/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

mortality/aging

premature death ( J:222375 )

• adult mice maintained off doxycline beyond the 3 week time point show increased mortality relative to age-matched on doxycline control mice

cardiovascular system

enlarged heart ( J:222375 )

• at 3 weeks off doxycline, adult mice exhibit dramatically enlarged hears relative to age-matched on doxycline control mice

myocardium hypertrophy ( J:222375 )

• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy

increased heart weight ( J:222375 )

• at 3 weeks off doxycycline, adult mice show a significantly increased heart mass and heart mass:body weight ratio relative to age-matched on doxycline control mice

• however, body weight is not significantly altered at 3 weeks off doxycycline

dilated cardiomyopathy ( J:222375 )

• at 1.5 and 3 weeks off doxycycline, adult mice display dilated cardiomyopathy (DCM), unlike age-matched on doxycline control mice

• DCM is more pronounced at 3 weeks off doxycycline

decreased heart left ventricle muscle contractility ( J:222375 )

• at 3 weeks off doxycline, adult mice show significantly reduced left ventricular ejection fraction (LVEF) and fractional shortening (%FS) relative to age-matched on doxycline control mice

abnormal heart echocardiography feature ( J:222375 )

• M-mode echocardiography revealed a significant increase in the chamber cavity (left ventricular internal diameter, systolic [LVIDs] and LVID, diastolic [LVIDd]), left ventricular mass (LVM) and LVM/body weight ratio, and a marked decrease in LVEF and %FS in mice off doxycycline for 1.5 and 3 weeks relative to age-matched on doxycline control mice

abnormal myocardial fiber physiology ( J:222375 )

• electrophysiological analysis of native volume-sensitive chloride channels (VSOACs) in isolated atrial and ventricular myocytes 3 weeks off doxycycline revealed a complete elimination of hypotonic-induced VSOAC currents, whereas at 1.5 weeks, VSOAC current densities are significantly reduced, relative to age-matched on doxycycline controls; no difference in current densities are noted under isotonic conditions prior to cell swelling

• membrane capacitance is significantly increased in ventricular myocytes from mice 3 weeks off doxyclycline relative to ventricular myocytes from on doxycycline control mice; however, no difference in membrane capacitance is noted in atrial myocytes at 3 weeks off doxycycline

• at 1.5 weeks off doxycycline, residual hypotonic-induced VSOAC currents are totally abolished in isolated atrial myocytes by perfusion of 100 nM PDBu (a protein kinase C activator), similar to VSOAC currents in atrial cells from on doxycycline control mice

congestive heart failure ( J:222375 )

• at 3 weeks off doxycline, adult mice display severe signs of heart failure

muscle

myocardium hypertrophy ( J:222375 )

• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy

dilated cardiomyopathy ( J:222375 )

• at 1.5 and 3 weeks off doxycycline, adult mice display dilated cardiomyopathy (DCM), unlike age-matched on doxycline control mice

• DCM is more pronounced at 3 weeks off doxycycline

decreased heart left ventricle muscle contractility ( J:222375 )

• at 3 weeks off doxycline, adult mice show significantly reduced left ventricular ejection fraction (LVEF) and fractional shortening (%FS) relative to age-matched on doxycline control mice

growth/size/body

enlarged heart ( J:222375 )

• at 3 weeks off doxycline, adult mice exhibit dramatically enlarged hears relative to age-matched on doxycline control mice

myocardium hypertrophy ( J:222375 )

• at 3 weeks off doxycline, adult mice display severe signs of myocardial hypertrophy

increased heart weight ( J:222375 )

• at 3 weeks off doxycycline, adult mice show a significantly increased heart mass and heart mass:body weight ratio relative to age-matched on doxycline control mice

• however, body weight is not significantly altered at 3 weeks off doxycycline

Genotype
MGI:5502430

cn3

• Allelic Composition: Kras^tm1Bbd/Kras^tm1Bbd; Tg(Cela1-tTA)#Eps/?; Tg(tetO-cre)3Jig/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/N

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:119988 )

• focal morphological lesions develop in acinar and centroacinar cells at 1-3 months

• acinar to ductal metaplasias develop

• some mice develop ductal adenocarcinomas by 12 months

• properties are similar to those in human patients

• sometimes areas of non malignant hyperplasia develop

increased tumor latency ( J:119988 )

• latency is increased if gene expression is delayed by maintaining exposure to doxycycline until 10 days of age

• if doxycycline exposure continues to 2 months of age, no pancreatic abnormalities develop

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:119988 )

• sometimes areas of non malignant hyperplasia develop

• focal morphological lesions develop in acinar and centroacinar cells at 1-3 months

• acinar to ductal metaplasias develop

• some mice develop ductal adenocarcinomas by 12 months

• properties are similar to those in human patients

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:119988