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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(Ins2-rtTA)2Efr
transgene insertion 2, Shimon Efrat
MGI:3770667
Summary 8 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Tg(CAG-Bgeo/ALPP)1Lbe/0
Tg(Ins2-cre/ERT)1Dam/0
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-DTA)1Gfi/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA MGI:3770687
cx2
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-TAg)1Efr/0
involves: C3HeB/FeJ * C57BL/6 * CBA MGI:3770671
cx3
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Mir184)#Mnpy/0
involves: C57BL/6 * CBA MGI:5585178
cx4
Lepob/Lepob
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Mir184)#Mnpy/0
involves: C57BL/6 * CBA MGI:5585179
cx5
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Ago2)30Mnpy/0
involves: C57BL/6 * CBA MGI:5585183
cx6
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Sri)1Hhv/0
involves: C57BL/6 * CBA MGI:6160821
cx7
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Sri)10Hhv/0
involves: C57BL/6 * CBA MGI:6160822
cx8
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-DTA)1Gfi/0
involves: C57BL/6 * CBA MGI:3770688


Genotype
MGI:3770687
cn1
Allelic
Composition
Tg(CAG-Bgeo/ALPP)1Lbe/0
Tg(Ins2-cre/ERT)1Dam/0
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-DTA)1Gfi/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(CAG-Bgeo/ALPP)1Lbe mutation (1 available)
Tg(Ins2-cre/ERT)1Dam mutation (2 available)
Tg(Ins2-rtTA)2Efr mutation (2 available)
Tg(tetO-DTA)1Gfi mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• tamoxifen injections during last 10 days of doxycycline treatment labels surviving beta cells with human placental alkaline phosphatase; labeling results indicate that majority or all regenerated beta cells are derived from surviving beta cells, rather than from non-beta cells or stem cells

homeostasis/metabolism
• treatment of newborn mice with doxycycline for 45 days results in diabetes development




Genotype
MGI:3770671
cx2
Allelic
Composition
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-TAg)1Efr/0
Genetic
Background
involves: C3HeB/FeJ * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ins2-rtTA)2Efr mutation (2 available)
Tg(tetO-TAg)1Efr mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• hypoglycemic mice are observed to have multiple insulinomas in pancreas

homeostasis/metabolism
N
• in presence of doxycycline, strepzotocin-treated mice transplanted with beta cells isolated from insulinomas from double-transgenic mice display euglycemia within one day of transplantation; blood glucose levels remained in euglycemic range for >6 weeks after doxycycline withdrawal
• mice receiving doxycycline in drinking water to induce transgene expression develop hypoglycemia by 3-4 months of age; mutants not treated with doxycycline remain euglycemic and have normal islet morphology

neoplasm
• hypoglycemic mice are observed to have multiple insulinomas in pancreas




Genotype
MGI:5585178
cx3
Allelic
Composition
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Mir184)#Mnpy/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ins2-rtTA)2Efr mutation (2 available)
Tg(tetO-Mir184)#Mnpy mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• in doxycycline-treated mice
• in doxycycline-treated mice
• in doxycycline-treated mice

homeostasis/metabolism
• in doxycycline-treated mice
• in doxycycline-treated mice
• in doxycycline-treated mice

cellular
• in doxycycline-treated mice




Genotype
MGI:5585179
cx4
Allelic
Composition
Lepob/Lepob
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Mir184)#Mnpy/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lepob mutation (5 available); any Lep mutation (17 available)
Tg(Ins2-rtTA)2Efr mutation (2 available)
Tg(tetO-Mir184)#Mnpy mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• in doxycycline-treated mice
• in doxycycline-treated mice




Genotype
MGI:5585183
cx5
Allelic
Composition
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Ago2)30Mnpy/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ins2-rtTA)2Efr mutation (2 available)
Tg(tetO-Ago2)30Mnpy mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• in doxycycline-treated mice
• in doxycycline-treated mice
• in doxycycline-treated mice
• doxycycline-treated mice exhibit reduced acute-phase plasma insulin release compared with control mice

homeostasis/metabolism
N
• doxycycline-treated mice exhibit normal insulin sensitivity after glucose challenge
• doxycycline-treated mice exhibit reduced acute-phase plasma insulin release compared with control mice
• transient after glucose challenge in doxycycline-treated mice

cellular
• in doxycycline-treated mice




Genotype
MGI:6160821
cx6
Allelic
Composition
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Sri)1Hhv/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ins2-rtTA)2Efr mutation (2 available)
Tg(tetO-Sri)1Hhv mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• in glucose-stimulation in doxycycline-treated male mice and ex vivo islets
• in doxycycline-treated male mice fed a high-fat diet
• however, insulin sensitivity is normal

endocrine/exocrine glands
• islet cells from doxycycline-treated male mice fed a high-fat diet exhibit improved cytosolic calcium fluxes and increased endoplasmic calcium stores

growth/size/body
N
• doxycycline-treated male mice exhibit normal weight change in response to being fed a high-fat diet




Genotype
MGI:6160822
cx7
Allelic
Composition
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-Sri)10Hhv/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ins2-rtTA)2Efr mutation (2 available)
Tg(tetO-Sri)10Hhv mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• in doxycycline-treated male mice fed a high-fat diet
• in glucose-stimulation in doxycycline-treated male mice and ex vivo islets
• in doxycycline-treated male mice fed a high-fat diet
• however, insulin sensitivity is normal

endocrine/exocrine glands
• doxycycline-treated male mice exhibit a decrease in beta to alpha cell compared with control mice
• however, mice exhibit normal mean pancreas surface, islet size, individual beta-cell or alpha-cell mass
• islet cells from doxycycline-treated male mice fed a high-fat diet exhibit improved cytosolic calcium fluxes and increased endoplasmic calcium stores

growth/size/body
N
• doxycycline-treated male mice exhibit normal weight change in response to being fed a high-fat diet




Genotype
MGI:3770688
cx8
Allelic
Composition
Tg(Ins2-rtTA)2Efr/0
Tg(tetO-DTA)1Gfi/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ins2-rtTA)2Efr mutation (2 available)
Tg(tetO-DTA)1Gfi mutation (3 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
N
• average size of regenerating beta cells is same as original cells
• pancreatic insulin content is reduced by ~85%; after doxycycline withdrawal, pancreatic insulin level return to near control levels
• frequency of insulin-positive, glucagons-positive beta cells increases from 1:5500 in controls to 1:1000 beta cells in diabetic transgenic mice
• permitting doxycycline-treated mice to recover in presence of immunosupressants Sirolimus and Tacrolimus (SirTac) significantly reduces beta cell proliferation and beta cell mass does not increase as it does in absence of immunosupressants; blood glucose levels in treated mice fail to normalize as they do in controls treated with SirTac
• 70-80% of beta cells are lost in doxycycline-treated 5-week old double-transgenic mice relative to controls
• similar results are obtained when beta cells are ablated between birth and five weeks of age; beta cell mass normalizes within ~15 weeks of doxycycline withdrawal
• rate of beta cell apoptosis in recovering mice is not different from controls, but beta cell proliferation is increased 2-3-fold within 48 hours of onset of beta cell ablation; this increased proliferation rate is maintained for several weeks
• treatment of four-week old mice with doxycycline for 1 week results in severely disrupted islet architecture with non-beta cells at the core of shriveled islets rather than beta cells
• after withdrawal of doxycycline, normalization of islet architecture occurs in ~90% of islets

homeostasis/metabolism
N
• peripheral insulin sensitivity after beta cell regeneration is similar to controls after doxycycline withdrawal, beta cell mass in transgenic mice increases to levels comparable to wild-type
• blood glucose levels of treated mice are elevated to 300-600 mg/dl making the mice overtly diabetic; after withdrawal of doxycycline, blood glucose levels return to normal level
• mice that showed severe, chronic or adult-onset (starting at 4 months) hyperglycemia spontaneously normalized blood glucose levels and beta-cell mass after doxycycline withdrawal
• blood glucose levels are elevated to 300-600 mg/dl; after doxycycline withdrawal, remission of hyperglycemia occurs such that fed and fasting glucose levels normalize
• mice that showed severe, chronic or adult-onset (starting at 4 months) hyperglycemia spontaneously normalized blood glucose levels and beta-cell mass after doxycycline withdrawal
• after more than 8 months without doxycycline, glucose tolerance starts to recover
• similar results are obtained when beta cells are ablated between birth and five weeks of age; beta cell mass normalizes within ~15 weeks of doxycycline withdrawal
• mice that showed severe, chronic or adult-onset (starting at 4 months) hyperglycemia spontaneously normalized blood glucose levels and beta-cell mass after doxycycline withdrawal

cellular
• widespread pancreatic beta cell apoptosis is seen within 48 hours of doxycycline treatment of double-transgenic mice, but no apoptosis is observed in single transgenic littermates





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last database update
01/12/2022
MGI 6.17
The Jackson Laboratory