Tg(Myh6-tTA)6Smbf Transgene Detail MGI Mouse (MGI:2665551)

Tg(Myh6-tTA)6Smbf
Transgene Detail

Nomenclature

Symbol:	Tg(Myh6-tTA)6Smbf
Name:	transgene insertion 6, Section of Myocardial Biology - Fishman Lab
MGI ID:	MGI:2665551
Synonyms:	2.9alphatTA, alphaMHC-tTA, Tg(MHCAtTA)6Smbf
Transgene:	Tg(Myh6-tTA)6Smbf Location: unknown

Cardiac fibrosis and ventricle dilatation in Tg(Myh6-tTA)6Smbf/0 Tg(tetO-DTA)1Gfi/0 mice

Show the 1 image(s) involving this allele.

Transgene
origin

Strain of Origin:

(C57BL/6 x CBA)F1

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	The transgene consists of a rat Myh6 promoter and a tetracycline transactivator sequence. Transgene expression in cardiac tissue was confirmed by Northern blot analysis. 2.9 kb of rat Myh6 promoter sequences directs transgene expression in the heart starting at embryonic day E7.5. (J:82692)

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	tg3
cardiovascular system		√	√	√
abnormal myocardial fiber morphology		√
increased cardiomyocyte apoptosis				√
decreased myocardial fiber number				√
enlarged heart		√
increased heart weight		√
cardiac hypertrophy		√
decreased cardiac muscle contractility		√
abnormal impulse conducting system conduction		√		√
prolonged PQ interval		√
abnormal heart development			√
absent endocardial cushion			√
abnormal outflow tract development			√
abnormal endocardium morphology			√
abnormal heart atrium morphology				√
abnormal heart ventricle morphology				√
abnormal heart left ventricle morphology		√
thick ventricular wall		√
dilated heart ventricles				√
cardiac fibrosis				√
cardiac interstitial fibrosis		√
ventricular tachycardia				√
irregular heartbeat				√
atrial fibrillation				√
		tg1	tg2	tg3
homeostasis/metabolism				√
atrial thrombosis				√
		tg1	tg2	tg3
lethality/prenatal-perinatal				√
embryonic lethality during organogenesis				√
		tg1	tg2	tg3
life span/aging				√
premature death				√
		tg1	tg2	tg3
muscle		√		√
abnormal myocardial fiber morphology		√
increased cardiomyocyte apoptosis				√
decreased myocardial fiber number				√
decreased cardiac muscle contractility		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
tg1	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-Mir208a)#Dzw/0	involves: C3H * C57BL/6 * CBA
cardiovascular system abnormal myocardial fiber morphology (J:152696) cardiomyocytes are about 50% bigger than in controls enlarged heart (J:152696) a dramatic increase in size is seen at 4 months of age increased heart weight (J:152696) heart weight to body weight ratios are increased cardiac hypertrophy (J:152696) chambers are enlarged and ventricle walls are thickened suggesting hypertrophic growth abnormal heart left ventricle morphology (J:152696) left ventricle diameter is increased in diastole and systole thick ventricular wall (J:152696) cardiac interstitial fibrosis (J:152696) decreased cardiac muscle contractility (J:152696) a decrease in fractional shortening is detected at 3 and 7 months of age abnormal impulse conducting system conduction (J:152696) about 30% of mice show second degree AV blocks, in which one or more of the electrical impulses from the atria failed to pass through the AV node to the ventricles prolonged PQ interval (J:152696) at 7 months of age, prolongation of the PR interval is seen indicating a first degree atrioventricular (AV) block muscle abnormal myocardial fiber morphology (J:152696) cardiomyocytes are about 50% bigger than in controls decreased cardiac muscle contractility (J:152696) a decrease in fractional shortening is detected at 3 and 7 months of age
Genotype	Allelic Composition	Genetic Background
tg2	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-Vegfa)1Kesh/0	involves: C57BL/6 * CBA
cardiovascular system abnormal heart development (J:68214) exhibit abnormal cardiac development upon tetracycline treatment to induce early expression of Vegfa absent endocardial cushion (J:68214) mesenchymal transformation and cellularization of the cardiac jelly are completely blocked in about half of E10.5 embryos abnormal outflow tract development (J:68214) outflow tract development is impaired with cardiac jelly remaining empty by the time it is colonized with mesenchymal cells in controls abnormal endocardium morphology (J:68214) multi-layered endocardium
Genotype	Allelic Composition	Genetic Background
tg3	Tg(Myh6-tTA)6Smbf/0 Tg(tetO-DTA)1Gfi/0	involves: C57BL/6 * CBA
Cardiac fibrosis and ventricle dilatation in Tg(Myh6-tTA)6Smbf/0 Tg(tetO-DTA)1Gfi/0 mice lethality/prenatal-perinatal embryonic lethality during organogenesis (J:128617) in absence of maternal supplementation with tetracycline (Tc) during gestation, no binary (or double) transgenic offspring are born, whereas gestational or perinatal suppressive Tc treatment results in Mendelian numbers of binary offspring (22%) genotypic analysis at times throughout gestation show that death of double transgenic embryos occurs between 10.5 days post conception (dpc) and fetal day 19 life span/aging premature death (J:128617) when Tc treatment is withdrawn after birth, mortality results with median survival time of 37 days (earliest time of death is 12 days after withdrawal of Tc, latest death is 77 days); death occurs suddenly with no indication of illness cardiovascular system increased cardiomyocyte apoptosis (J:128617) some hearts display severe cell loss following tetracycline withdrawal decreased myocardial fiber number (J:128617) hearts show evidence of mild to severe myocyte loss abnormal heart atrium morphology (J:128617) atrial tissue destruction is seen in some hearts abnormal heart ventricle morphology (J:128617) ventricles show patchy fibrosis following Tc withdrawal dilated heart ventricles (J:128617) in some hearts, prominent ventricular dilatation is observed following Tc withdrawal cardiac fibrosis (J:128617) ventricles show mild patchy fibrosis to severe fibrosis following Tc withdrawal ventricular tachycardia (J:128617) at 1 month after Tc withdrawal, most isolated-perfused hearts display either spontaneous or inducible ventricular tachycardia, including both sustained and nonsustained runs of ventricular tachycardia with some episodes lasting irregular heartbeat (J:128617) following Tc withdrawal, a variety of arrhythmias are detected in double transgenic mice which show increased propensity to develop reentrant tachycardia, including atrial fibrillation, pauses, and complex ventricular ectopy such as runs of ventricular tachycardia majority of even mildly diseased hearts are arrhythmogenic atrial fibrillation (J:128617) following tetracycline withdrawal, atrial fibrillation occurs in some mice abnormal impulse conducting system conduction (J:128617) at 1 month after tetracycline withdrawal, a subset of isolated-perfused hearts display markedly disturbed activation profiles, with either disorganized conduction or evidence of block during pacing majority of even mildly diseased hearts are arrhythmogenic muscle increased cardiomyocyte apoptosis (J:128617) some hearts display severe cell loss following tetracycline withdrawal decreased myocardial fiber number (J:128617) hearts show evidence of mild to severe myocyte loss homeostasis/metabolism atrial thrombosis (J:128617) mural thrombus formation is prominent in atrial tissue in some animals following Tc withdrawal

Notes

Transgenic line 6 showed the strongest cardiac transgene expression and was used for analysis.

References

Original:	J:82692 Yu Z et al., "Conditional transgene expression in the heart." Circ Res 1996 Oct;79(4):691-7
All:	25 reference(s)

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