Tg(INS-MT2A,Tyr)1Pne Transgene Detail MGI Mouse (MGI:3044323)

Tg(INS-MT2A,Tyr)1Pne
Transgene Detail

Nomenclature

Symbol:	Tg(INS-MT2A,Tyr)1Pne
Name:	transgene insertion 1, Paul N Epstein
MGI ID:	MGI:3044323
Synonyms:	HMT-1
Transgene:	Tg(INS-MT2A,Tyr)1Pne Location: unknown

Transgene
origin

Strain of Origin:

FVB

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	This transgene expresses the full length human metallothionein II gene under the control of the human insulin promoter and first intron. A second transgene that expresses tyrosinase under the control of the tyrosinase promoter was coinjected with the first transgene, and appears to cosegregate. (J:90564)

Find Mice (IMSR)

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

Carrying this Mutation:

Mouse Strains: 1 strain 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
digestive/alimentary system		√	√
abnormal pancreatic islet morphology		√	√
decreased pancreatic beta cell number			√
abnormal pancreas physiology		√
		tg1	tg2
endocrine/exocrine glands		√	√
abnormal pancreatic islet morphology		√	√
decreased pancreatic beta cell number			√
abnormal pancreas physiology		√
		tg1	tg2
homeostasis/metabolism		√	√
hyperglycemia		√
abnormal enzyme/ coenzyme level		√
decreased physiological sensitivity to xenobiotics		√	√
		tg1	tg2
immune system		√
abnormal response to transplant		√

		tg1	tg2
Disease Models		√	√
Diabetes Mellitus, Insulin-Dependent; IDDM		√	√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

tg1 Disease Model

Tg(INS-MT2A,Tyr)1Pne/0

FVB-Tg(INS-MT2A,Tyr)1Pne

homeostasis/metabolismhyperglycemia (J:90564)

after a single dose of streptozocin, control animals become hyperglycemic (>400mg/dl) after 2 days, while transgenic animals do not acquire a similar degree of diabetes during the 6 days of observation

abnormal enzyme/ coenzyme level (J:90564)

islets from transgenic mice have 30-fold higher levels of metallothionein compared to control islets from FVB mice

decreased physiological sensitivity to xenobiotics (J:90564)

cultured transgenic islets are relatively protected from damage by streptozocin compared to control islets; control islets are visibly damaged by 0.25 mmol/l and disintegrate into single cells by 0.5 mmol/l streptozocin but transgenic islets don't exhibit a similar level of damage until exposure to a dose of 1 mmol/l

transgenic islets have an increased threshold for DNA damage by streptozocin compared to control FVB islets

immune systemabnormal response to transplant (J:95089)

transgenic islets transferred into streptozocin-induced diabetic BALB/c mice are able to maintain almost normal blood glucose levels for over 16 days in recipients, while control islets could maintain euglycemia for just over 8 days

endocrine/exocrine glandsabnormal pancreatic islet morphology (J:95089)

islets are resistant to morphological damage and cell death induced by incubation with SNAP, a nitric oxide donor; FVB control islets are damaged under the same conditions

after transplantation of transgenic islet or control iset grafts into FVB recipients, after 6 days transgenic islets retain 60% of their original insulin content while control islets only retain less than 20% ot their initial insulin

abnormal pancreas physiology (J:95089)

transgenic islets produce a lower level of reactive oxygen species after 7 hours of hypoxia than conrol islet cells

digestive/alimentary systemabnormal pancreatic islet morphology (J:95089)

islets are resistant to morphological damage and cell death induced by incubation with SNAP, a nitric oxide donor; FVB control islets are damaged under the same conditions

abnormal pancreas physiology (J:95089)

transgenic islets produce a lower level of reactive oxygen species after 7 hours of hypoxia than conrol islet cells

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Diabetes Mellitus, Insulin-Dependent; IDDM		J:100251

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

tg2 Disease Model

Tg(INS-MT2A,Tyr)1Pne/0

NOD.FVB-Tg(INS-MT2A,Tyr)1Pne

homeostasis/metabolismdecreased physiological sensitivity to xenobiotics (J:108415)

treatment of transgenic NOD mice with cyclophosphamide (CYP) accelerated NOD diabetes; 20 days after injection of CYP 93% of transgenic mice are diabetic compared with 7% of treated controls

transgenic mice on the FVB background do not develop diabetes with the same regimen of CYP treatment as the NOD transgenic mice

transgenic mice exhibit greater resistance to induced diabetes after treatment with streptozotocin compared with NOD controls

endocrine/exocrine glandsabnormal pancreatic islet morphology (J:108415)

8 days after CYP treatment significantly more islets of transgenic NOD mice appear small and disrupted compared to treated NOD controls; percentages of damaged areas (Caspase-3 positive) in islets are 11.7 and 5.5% in transgenic NOD and control NOD mice respectively

cultured islets of transgenic NOD mice are more sensitive to a mix of cytokines (Il-beta, Tnfa and Ifng) than NOD control islets as revealed by Caspase-3 activity

decreased pancreatic beta cell number (J:108415)

beta cell damage is significantly increased in transgenic mice after CYP injection compared to controls; pancreatic insulin content is only 36% of original level after 8 days compared to 76% in control NOD mice

digestive/alimentary systemabnormal pancreatic islet morphology (J:108415)

cultured islets of transgenic NOD mice are more sensitive to a mix of cytokines (Il-beta, Tnfa and Ifng) than NOD control islets as revealed by Caspase-3 activity

decreased pancreatic beta cell number (J:108415)

Mouse Models of Human Disease	Note	Ref(s)
Models involving transgenes or other mutation types.¹
Diabetes Mellitus, Insulin-Dependent; IDDM		J:108415

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
			Allelic Composition	Genetic Background
Models involving transgenes or other mutation types.¹
Diabetes Mellitus, Insulin-Dependent; IDDM OMIM ID: 222100		tg2	Tg(INS-MT2A,Tyr)1Pne/0	NOD.FVB-Tg(INS-MT2A,Tyr)1Pne	J:108415
		tg1	Tg(INS-MT2A,Tyr)1Pne/0	FVB-Tg(INS-MT2A,Tyr)1Pne	J:100251

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

References

Original:	J:90564 Chen H et al., "Overexpression of metallothionein in pancreatic beta-cells reduces streptozotocin-induced DNA damage and diabetes." Diabetes 2001 Sep;50(9):2040-6
All:	4 reference(s)

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