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Phenotypes Associated with This Genotype
Genotype
MGI:5604242
Allelic
Composition
Tg(Myh6-rtTA)8585Jam/0
Tg(tetO-Fgfr3*R248C/Fgfr1)#Dor/0
Genetic
Background
involves: 129 * C57BL/6 * FVB/N * FVB/NTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Myh6-rtTA)8585Jam mutation (1 available)
Tg(tetO-Fgfr3*R248C/Fgfr1)#Dor mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cardiovascular system
• progressively increasing myocyte size with DOX treatment
• cardiomyocyte cross-sectional area is increased by one week of DOX treatment and continues to increase through 6 months of DOX induction
• cardiomyocyte cross-sectional area is reduced by 24% after DOX removal but remains larger than controls
• patchy areas of myocyte disarray are seen after 42 days of DOX treatment
• following 42 days of DOX treatment, hearts are larger and this increase is even more apparent after 300 days of DOX treatment
• mice show progressive development of cardiac concentric hypertrophy with preservation of systolic function from baseline through 6 months of DOX induction
• mice exhibit an elevation of left ventricle mass index by one week of DOX induction
• after 10 months of DOX treatment, concentric hypertrophy is still present, without any progression to left ventricle dilatation
• both treatment with losartan and propranolol one week prior to the start of DOX and continued throughout one week of induction abrogate the hypertrophic response (left ventricle mass index) and moderately block the increase in left ventricle posterior wall thickness
• dynamic obstruction in the proximal left ventricle is seen with six weeks of DOX treatment
• mice exhibit an increase in left ventricle diastolic posterior wall thickness within one day of DOX induction; the wall thickness is concentric and symmetrical
• left ventricle diastolic posterior wall thickness is reduced by 16% after DOX removal, but remains elevated
• increase in interstitial fibrosis is seen after 42 days of DOX treatment
• end systolic volume and end diastolic volume are decreased within one day of DOX induction
• slope of the end systolic pressure-volume relationship is elevated within 24 hours of DOX induction
• ventricular myocytes treated with DOX for 1-2 days have shorter lengths at both diastole and systole, with an overall increase in fractional shortening, indicating impaired relaxation and enhanced contraction of cardiomyocytes
• mice show an increase in contractility following DOX treatment, as evidenced by an elevated slope of the end-systolic pressure-volume relationship between the baseline and increased afterload pressure-volume following constriction of the transverse aorta
• mice treated with DOX for six weeks show elevated late-peaking outflow velocities compared to non-DOX treated mice
• in the absence of doxycycline (DOX), mice show a small, but significant, increase in left ventricle peak outflow velocity, however cardiac mass, myocyte size and left ventricle wall thickness are normal, indicating increased contractility but no hypertrophy at baseline
• left ventricle peak outflow velocity measured at the point of flow convergence in the mid-ventricle decreases by 20% after DOX removal but remains elevated compared to controls
• treatment with propranolol one week prior to the start of DOX and continued throughout one week of induction reduces the dynamic obstruction as measured by left ventricle outflow velocity but not completely
• left ventricle internal diastolic diameter is decreased within one week of DOX induction
• left ventricle mass index and left ventricle internal diastolic diameter returns to near control levels after DOX removal
• treatment with DOX leads to hypertrophic cardiomyopathy

growth/size/body
• following 42 days of DOX treatment, hearts are larger and this increase is even more apparent after 300 days of DOX treatment
• mice show progressive development of cardiac concentric hypertrophy with preservation of systolic function from baseline through 6 months of DOX induction
• mice exhibit an elevation of left ventricle mass index by one week of DOX induction
• after 10 months of DOX treatment, concentric hypertrophy is still present, without any progression to left ventricle dilatation
• both treatment with losartan and propranolol one week prior to the start of DOX and continued throughout one week of induction abrogate the hypertrophic response (left ventricle mass index) and moderately block the increase in left ventricle posterior wall thickness

muscle
• progressively increasing myocyte size with DOX treatment
• cardiomyocyte cross-sectional area is increased by one week of DOX treatment and continues to increase through 6 months of DOX induction
• cardiomyocyte cross-sectional area is reduced by 24% after DOX removal but remains larger than controls
• patchy areas of myocyte disarray are seen after 42 days of DOX treatment
• mice show an increase in contractility following DOX treatment, as evidenced by an elevated slope of the end-systolic pressure-volume relationship between the baseline and increased afterload pressure-volume following constriction of the transverse aorta
• mice treated with DOX for six weeks show elevated late-peaking outflow velocities compared to non-DOX treated mice
• in the absence of doxycycline (DOX), mice show a small, but significant, increase in left ventricle peak outflow velocity, however cardiac mass, myocyte size and left ventricle wall thickness are normal, indicating increased contractility but no hypertrophy at baseline
• left ventricle peak outflow velocity measured at the point of flow convergence in the mid-ventricle decreases by 20% after DOX removal but remains elevated compared to controls
• treatment with propranolol one week prior to the start of DOX and continued throughout one week of induction reduces the dynamic obstruction as measured by left ventricle outflow velocity but not completely
• left ventricle internal diastolic diameter is decreased within one week of DOX induction
• left ventricle mass index and left ventricle internal diastolic diameter returns to near control levels after DOX removal
• treatment with DOX leads to hypertrophic cardiomyopathy

behavior/neurological
N
• mice fed DOX for 6 months show normal exercise tolerance

cellular
• increase in interstitial fibrosis is seen after 42 days of DOX treatment

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
hypertrophic cardiomyopathy DOID:11984 J:211151


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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
11/12/2024
MGI 6.24
The Jackson Laboratory