Phenotypes associated with this allele

• Allele Symbol: Med30^tm1.1Sev
• Allele Name: targeted mutation 1.1, Sylvia Evans
• Allele ID: MGI:7314487
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Med30^tm1.1Sev/Med30^tm1.1Sev	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:7314614
cn2	Med30^tm1.1Sev/Med30^tm1.1Sev Tg(Tnnt2-cre)5Blh/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2 * SJL	MGI:7314618
cn3	Med30^tm1.1Sev/Med30^tm1.1Sev A1cf^Tg(Myh6-cre/Esr1*)1Jmk/A1cf^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N * SJL	MGI:8293405

Genotype
MGI:7314614

hm1

• Allelic Composition: Med30^tm1.1Sev/Med30^tm1.1Sev
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

normal phenotype

no abnormal phenotype detected ( J:309620 )

• mice are viable and born at expected Mendelian ratios with no apparent defects

Genotype
MGI:7314618

cn2

• Allelic Composition: Med30^tm1.1Sev/Med30^tm1.1Sev; Tg(Tnnt2-cre)5Blh/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2 * SJL

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:309620 )

• only 2 out of 30 embryos are dead at E11.5; by E12.5, all embryos are either found dead or partially resorbed and no live mice are recovered at P1

cardiovascular system

abnormal heart development ( J:309620 )

• at E11.5, embryos show severe cardiac developmental defects

• however, at E10.5, embryos are grossly indistinguishable from controls

small heart ( J:309620 )

• at E11.5, four out of 30 embryos have smaller hearts

thin left ventricle myocardium compact layer ( J:309620 )

• at E11.5, the thickness of the compact zone in the left ventricle (LV) is severely decreased

• however, LV compact zone thickness is normal at E10.5

thin right ventricle myocardium compact layer ( J:309620 )

• at E11.5, the thickness of the compact zone in the right ventricle (RV) is severely decreased

• however, RV compact zone thickness is normal at E10.5

thin ventricular wall ( J:309620 )

• at E11.5, twenty out of 30 embryos exhibit thinner ventricular walls

internal hemorrhage ( J:309620 )

• at E11.5, seven out of 30 embryos show hemorrhage

decreased fetal cardiomyocyte proliferation ( J:309620 )

• at E9.5, the % of EdU+ cardiomyocytes starts to decrease in the compact zone of the LV, whereas trabecular cardiomyocytes and RV cardiomyocytes show no differences in EdU incorporation

• by E10.5, cardiomyocyte proliferation is severely decreased in the compact zone and trabeculae of both ventricles

• however, no apoptotic cardiomyocytes are detected in the heart at E11.5 by TUNEL staining

muscle

thin left ventricle myocardium compact layer ( J:309620 )

• at E11.5, the thickness of the compact zone in the left ventricle (LV) is severely decreased

• however, LV compact zone thickness is normal at E10.5

thin right ventricle myocardium compact layer ( J:309620 )

• at E11.5, the thickness of the compact zone in the right ventricle (RV) is severely decreased

• however, RV compact zone thickness is normal at E10.5

decreased fetal cardiomyocyte proliferation ( J:309620 )

• at E9.5, the % of EdU+ cardiomyocytes starts to decrease in the compact zone of the LV, whereas trabecular cardiomyocytes and RV cardiomyocytes show no differences in EdU incorporation

• by E10.5, cardiomyocyte proliferation is severely decreased in the compact zone and trabeculae of both ventricles

• however, no apoptotic cardiomyocytes are detected in the heart at E11.5 by TUNEL staining

homeostasis/metabolism

pleural effusion ( J:309620 )

• at E11.5, three out of 30 embryos show chest edema

decreased protein level ( J:309620 )

• heart tissue isolated from E10.5 embryos shows a significant decrease in the protein levels of most Mediator core subunits, except for MED1 and MED4 within the Middle submodule

• at E11.5, cardiac protein levels of MED4 are significantly decreased, possibly reflecting a slower rate of degradation, while protein levels of MED1 remain unaltered

• although total MED1 protein levels are normal at E10.5, the level of MED1 present in MED4 and MED12 immunoprecipitates is significantly reduced in hearts, suggesting that the preserved MED1 is not associated with the Mediator complex

• notably, kinase module members MED12 and MED13 are not changed in the heart at either E10.5 or E11.5

• moreover, transcript levels of the examined Mediator subunits are not reduced at E10.5

cellular

decreased fetal cardiomyocyte proliferation ( J:309620 )

• at E9.5, the % of EdU+ cardiomyocytes starts to decrease in the compact zone of the LV, whereas trabecular cardiomyocytes and RV cardiomyocytes show no differences in EdU incorporation

• by E10.5, cardiomyocyte proliferation is severely decreased in the compact zone and trabeculae of both ventricles

• however, no apoptotic cardiomyocytes are detected in the heart at E11.5 by TUNEL staining

respiratory system

pleural effusion ( J:309620 )

• at E11.5, three out of 30 embryos show chest edema

Genotype
MGI:8293405

cn3

• Allelic Composition: Med30^tm1.1Sev/Med30^tm1.1Sev; A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N * SJL

mortality/aging

premature death ( J:309620 )

• mice begin to die at 23 days post-tamoxifen injection, with no mice surviving longer than 40 days post-tamoxifen injection

• survival is not prolonged when mice are fed a ketogenic diet beginning at the time of tamoxifen injection

cardiovascular system

thin ventricular wall ( J:309620 )

• mice show significantly thinner ventricular walls at 4 weeks, but not at 2 weeks, post-tamoxifen injection

decreased heart left ventricle posterior wall thickness ( J:309620 )

• at 4 weeks post-tamoxifen injection, LV posterior wall thickness at end-diastole (LVPWd) is significantly decreased

dilated heart ventricle ( J:309620 )

• mice show significantly dilated ventricular chambers at 4 weeks, but not at 2 weeks, post-tamoxifen injection

dilated heart left ventricle ( J:309620 )

• at 4 weeks post-tamoxifen injection, mice show LV chamber dilation, as shown by a significant increase in end-diastolic LV internal diameter (LVIDd) and end-systolic LV internal diameter (LVIDs)

• however, no change is observed in the LV weight to body weight (LV/BW) ratio or in the LV weight to tibial length (VW/TL) ratio at 4 weeks after tamoxifen injection

cardiac fibrosis ( J:309620 )

• at 4 weeks post-tamoxifen injection, hearts show significantly increased mRNA levels of the profibrotic genes Col1a1 and Col3a1

• although no cardiac fibrosis is detected by Masson's trichrome staining, significant activation of fibroblasts is observed by immunofluorescence staining for periostin, suggesting activation of fibrosis at 4 weeks post-tamoxifen injection

dilated cardiomyopathy ( J:309620 )

• mice show rapid development of dilated cardiomyopathy after tamoxifen injection

decreased heart left ventricle muscle contractility ( J:309620 )

• mice show a time-dependent decrease in left ventricular (LV) systolic function, with a significantly reduced % of fractional shortening (FS) at 4 weeks, but not at 2 weeks, post-tamoxifen injection

increased myocardial fiber apoptosis ( J:309620 )

• at 4 weeks post-tamoxifen injection, heart sections show a significant increase in the number of TUNEL+ cardiomyocytes

congestive heart failure ( J:309620 )

• at 4 weeks post-tamoxifen injection, hearts show significantly increased mRNA levels of the cardiac fetal gene markers atrial natriuretic factor (Nppa/Anf) and B-type natriuretic peptide (Nppb/Bnp), consistent with cardiac stress

muscle

dilated cardiomyopathy ( J:309620 )

• mice show rapid development of dilated cardiomyopathy after tamoxifen injection

decreased heart left ventricle muscle contractility ( J:309620 )

• mice show a time-dependent decrease in left ventricular (LV) systolic function, with a significantly reduced % of fractional shortening (FS) at 4 weeks, but not at 2 weeks, post-tamoxifen injection

increased myocardial fiber apoptosis ( J:309620 )

• at 4 weeks post-tamoxifen injection, heart sections show a significant increase in the number of TUNEL+ cardiomyocytes

homeostasis/metabolism

decreased protein level ( J:309620 )

• adult cardiomyocytes isolated at 4 weeks post-tamoxifen injection show a significant decrease in the protein levels of several Mediator core subunits, including subunits of the Tail submodule (MED16, MED24, MED29), Middle submodule (MED4, MED31 and MED14), and Head submodule (MED8, MED17 and MED18)

cellular

increased myocardial fiber apoptosis ( J:309620 )

• at 4 weeks post-tamoxifen injection, heart sections show a significant increase in the number of TUNEL+ cardiomyocytes