Phenotypes associated with this allele

• Allele Symbol: Med27^tm1.1Xfa
• Allele Name: targeted mutation 1.1, Xi Fang
• Allele ID: MGI:8291593
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Med27^tm1.1Xfa/Med27^tm1.1Xfa	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:8291799
cn2	Med27^tm1.1Xfa/Med27^tm1.1Xfa Tg(Tnnt2-cre)5Blh/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2 * SJL	MGI:8291801
cn3	Med27^tm1.1Xfa/Med27^tm1.1Xfa A1cf^Tg(Myh6-cre/Esr1*)1Jmk/A1cf^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N * SJL	MGI:8292496

Genotype
MGI:8291799

hm1

• Allelic Composition: Med27^tm1.1Xfa/Med27^tm1.1Xfa
• 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:379748 )

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

Genotype
MGI:8291801

cn2

• Allelic Composition: Med27^tm1.1Xfa/Med27^tm1.1Xfa; 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:379748 )

• 3 out of 13 embryos are dead at E12.5; by E13.5, all embryos are either found dead or partially resorbed and no live mice are recovered at P1

cardiovascular system

thin ventricle myocardium compact layer ( J:379748 )

• at E11.5, the thickness of the ventricular compact zone is significantly decreased

thin left ventricle myocardium compact layer ( J:379748 )

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

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

thin right ventricle myocardium compact layer ( J:379748 )

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

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

abnormal cardiovascular development ( J:379748 )

• by E12.5, embryos show severe morphological defects indicative of abnormal cardiovascular development

abnormal heart development ( J:379748 )

• abnormal cardiac development is accompanied by dysregulation of the transcriptional program

thin ventricular wall ( J:379748 )

• at E11.5

internal hemorrhage ( J:379748 )

• by E12.5, one out of 13 embryos exhibits hemorrhage

decreased fetal cardiomyocyte proliferation ( J:379748 )

• at E10.5, the % of EdU+ cardiomyocytes starts to decrease in the compact zone of the LV, while no significant differences are noted in trabecular cardiomyocytes and RV cardiomyocytes

• by E11.5, cardiomyocyte proliferation is significantly reduced in the compact zone of both ventricles

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

muscle

thin ventricle myocardium compact layer ( J:379748 )

• at E11.5, the thickness of the ventricular compact zone is significantly decreased

thin left ventricle myocardium compact layer ( J:379748 )

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

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

thin right ventricle myocardium compact layer ( J:379748 )

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

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

decreased fetal cardiomyocyte proliferation ( J:379748 )

• at E10.5, the % of EdU+ cardiomyocytes starts to decrease in the compact zone of the LV, while no significant differences are noted in trabecular cardiomyocytes and RV cardiomyocytes

• by E11.5, cardiomyocyte proliferation is significantly reduced in the compact zone of both ventricles

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

homeostasis/metabolism

pleural effusion ( J:379748 )

• at E11.5, three out of 68 embryos exhibit chest edema or signs of death; by E12.5, three out of 13 embryos exhibit chest edema

• however, embryos are grossly indistinguishable from control littermates at E10.5 and most exhibit no distinct morphology at E11.5

decreased protein level ( J:379748 )

• heart tissue isolated from E10.5 embryos shows a significant decrease in protein levels of several subunits of the Mediator complex, including subunits of the Tail Module (MED30, MED15, MED16), Middle Module (MED14), and Head Module (MED6, MED8, MED17, MED18, MED20)

• by E11.5, all subunits of the Mediator core detected in the Tail, Middle and Head Modules are significantly reduced, while the subunits of the Kinase Module (MED12 and MED13) show protein levels comparable to those in control hearts

• in culture, overexpression of exogenous MED30 (an Upper Tail subunit of the Mediator complex) via a BioID-tag fused MED30 adenovirus in E11.5 cardiomyocytes fails to rescue the protein levels of Mediator core subunits MED14 (Middle Module), MED15 (Tail Module) and MED17 (Head Module) at 72 h after virus treatment, suggesting that MED27 maintains the integrity/stability of the Mediator complex independently of MED30

• transcript levels of Mediator subunits -- including the subunits examined for protein levels in developing hearts -- are not altered, suggesting that Mediator core subunits decrease through a post-transcriptional mechanism

cellular

decreased fetal cardiomyocyte proliferation ( J:379748 )

• at E10.5, the % of EdU+ cardiomyocytes starts to decrease in the compact zone of the LV, while no significant differences are noted in trabecular cardiomyocytes and RV cardiomyocytes

• by E11.5, cardiomyocyte proliferation is significantly reduced in the compact zone of both ventricles

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

respiratory system

pleural effusion ( J:379748 )

• at E11.5, three out of 68 embryos exhibit chest edema or signs of death; by E12.5, three out of 13 embryos exhibit chest edema

• however, embryos are grossly indistinguishable from control littermates at E10.5 and most exhibit no distinct morphology at E11.5

Genotype
MGI:8292496

cn3

• Allelic Composition: Med27^tm1.1Xfa/Med27^tm1.1Xfa; A1cf^{Tg(Myh6-cre/Esr1*)1Jmk}/A1cf⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * FVB/N * SJL

mortality/aging

premature death ( J:379748 )

• mice begin to die as early as 29 days post-tamoxifen injection, with only 2 out of 12 surviving longer than 40 days post-tamoxifen injection

cardiovascular system

dilated heart ventricle ( J:379748 )

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

dilated heart left ventricle ( J:379748 )

♂ • at 4 weeks post-tamoxifen injection, male 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, LV posterior wall thickness at end-diastole (LVPWd) is not significantly altered, and no change in the ratio of ventricle weight to body weight (VW/BW) or ratio of ventricle weight to tibial length (VW/TL) is observed at 4 weeks after tamoxifen injection

cardiac fibrosis ( J:379748 )

♂ • at 4 weeks post-tamoxifen injection, mRNA levels of the profibrotic genes Col1a1 and Col3a1 are significantly increased in male hearts; cardiac fibrosis is increased, as assessed by Masson's trichrome staining

dilated cardiomyopathy ( J:379748 )

♂ • male mice develop dilated cardiomyopathy rapidly after tamoxifen injection

decreased heart left ventricle muscle contractility ( J:379748 )

♂ • at 4 weeks post-tamoxifen injection, male mice show a significant decrease in left ventricular (LV) systolic function, as indicated by a reduced % of fractional shortening (FS)

increased myocardial fiber apoptosis ( J:379748 )

♂ • at 4 weeks post-tamoxifen injection, an increased number of TUNEL+ cardiomyocytes is observed in male hearts

congestive heart failure ( J:379748 )

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

muscle

dilated cardiomyopathy ( J:379748 )

♂ • male mice develop dilated cardiomyopathy rapidly after tamoxifen injection

decreased heart left ventricle muscle contractility ( J:379748 )

♂ • at 4 weeks post-tamoxifen injection, male mice show a significant decrease in left ventricular (LV) systolic function, as indicated by a reduced % of fractional shortening (FS)

increased myocardial fiber apoptosis ( J:379748 )

♂ • at 4 weeks post-tamoxifen injection, an increased number of TUNEL+ cardiomyocytes is observed in male hearts

homeostasis/metabolism

decreased protein level ( J:379748 )

♂ • adult cardiomyocytes isolated from male hearts at 4 weeks post-tamoxifen injection show a significant decrease in the protein levels of several Mediator core subunits, including subunits of the Tail Module (MED15, MED16), Middle Module (MED1 and MED31), and Head Module (MED17, MED18, MED20)

♂ • transcript levels of Mediator subunits -- including the subunits examined for protein levels in adult cardiomyocytes -- are not altered, suggesting that Mediator core subunits decrease through a post-transcriptional mechanism

cellular

increased myocardial fiber apoptosis ( J:379748 )

♂ • at 4 weeks post-tamoxifen injection, an increased number of TUNEL+ cardiomyocytes is observed in male hearts