Tg(Ins2-rtTA)2Efr Transgene Detail MGI Mouse (MGI:3770667)

Tg(Ins2-rtTA)2Efr
Transgene Detail

Nomenclature

Symbol:	Tg(Ins2-rtTA)2Efr
Name:	transgene insertion 2, Shimon Efrat
MGI ID:	MGI:3770667
Synonyms:	Ins-rtTA, RIP7-rtTA, RiprtTA
Transgene:	Tg(Ins2-rtTA)2Efr Location: unknown

Transgene
origin

Strain of Origin:

(C57BL/6 x CBA)F2

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	A transgenic construct containing 9.5kb 5' regulatory sequence and first intron of the rat insulin 2 gene (RIP7) controlling the reverse tetracycline transactivator (rtTA), as well as the polyadenylation site sequence of the RIP7 gene was injected into fertilized (C57BL/6 X CBA)F2 mouse eggs. Founder line 2 with 10 copies of the transgene was established. When mice are crossed to transgenic mice carrying reporter genes, transgene expression is detected only in pancreatic islet beta cells. (J:130049)

Find Mice (IMSR)

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

Carrying this Mutation:

Mouse Strains: 2 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:	tg1	tg2	tg3
cellular				√
increased apoptosis				√
		tg1	tg2	tg3
digestive/alimentary system		√		√
abnormal pancreas morphology				√
abnormal pancreatic beta cell morphology				√
increased pancreatic beta cell number		√		√
decreased pancreatic beta cell number				√
disorganized pancreatic islets				√
		tg1	tg2	tg3
endocrine/exocrine glands		√		√
endocrine/exocrine glands phenotype				N
abnormal pancreas morphology				√
abnormal pancreatic beta cell morphology				√
increased pancreatic beta cell number		√		√
decreased pancreatic beta cell number				√
disorganized pancreatic islets				√
		tg1	tg2	tg3
homeostasis/metabolism		√	√	√
homeostasis/metabolism phenotype			N	N
hypoglycemia			√
increased circulating glucose level				√
hyperglycemia		√		√
improved glucose tolerance				√
		tg1	tg2	tg3
tumorigenesis			√
insulinoma			√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
tg1	Tg(CAG-Bgeo/ALPP)1Lbe/0 Tg(Ins2-cre/Esr1)1Dam/0 Tg(Ins2-rtTA)2Efr/0 Tg(tetO-DTA)1Gfi/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
digestive/alimentary system increased pancreatic beta cell number (J:127412) 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 endocrine/exocrine glands increased pancreatic beta cell number (J:127412) 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 hyperglycemia (J:127412) treatment of newborn mice with doxycycline for 45 days results in diabetes development
Genotype	Allelic Composition	Genetic Background
tg2	Tg(Ins2-rtTA)2Efr/0 Tg(tetO-TAg)1Efr/0	involves: C3HeB/FeJ * C57BL/6 * CBA
homeostasis/metabolism homeostasis/metabolism phenotype (J:130049) 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 hypoglycemia (J:130049) 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 tumorigenesis insulinoma (J:130049) hypoglycemic mice are observed to have multiple insulinomas in pancreas
Genotype	Allelic Composition	Genetic Background
tg3	Tg(Ins2-rtTA)2Efr/0 Tg(tetO-DTA)1Gfi/0	involves: C57BL/6 * CBA
endocrine/exocrine glands endocrine/exocrine gland phenotype (J:127412) average size of regenerating beta cells is same as original cells abnormal pancreas morphology (J:127412) pancreatic insulin content is reduced by ~85%; after doxycycline withdrawal, pancreatic insulin level return to near control levels abnormal pancreatic beta cell morphology (J:127412) 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 decreased pancreatic beta cell number (J:127412) 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 increased pancreatic beta cell number (J:127412) 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 disorganized pancreatic islets (J:127412) 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 digestive/alimentary system abnormal pancreas morphology (J:127412) pancreatic insulin content is reduced by ~85%; after doxycycline withdrawal, pancreatic insulin level return to near control levels abnormal pancreatic beta cell morphology (J:127412) 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 decreased pancreatic beta cell number (J:127412) 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 increased pancreatic beta cell number (J:127412) 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 disorganized pancreatic islets (J:127412) 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 homeostasis/metabolism phenotype (J:127412) 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 increased circulating glucose level (J:127412) 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 hyperglycemia (J:127412) 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 improved glucose tolerance (J:127412) 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 increased apoptosis (J:127412) 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

References

Original:	J:130049 Milo-Landesman D et al., "Correction of hyperglycemia in diabetic mice transplanted with reversibly immortalized pancreatic beta cells controlled by the tet-on regulatory system." Cell Transplant 2001;10(7):645-50
All:	5 reference(s)

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