Phenotypes for Rxra MGI:2176443 MGI Mouse

lethality throughout fetal growth and development, complete penetrance ( J:18047 )

• homozygotes die between E13.5 and E16.5, with most embryos still viable at E14.5 but dead by E15.5

abnormal truncus arteriosus septation ( J:18047 )

• at E14.5, only 1 of 10 homozygotes displays an abnormal aortic pulmonary septum; both aortic and pulmonary valves appear unaffected

abnormal heart morphology ( J:65904 )

• at E13.5, upon color fluorescent imaging, the mutant heart appears much more translucent than the wild-type heart

aortopulmonary window ( J:35363 )

• 28% show incomplete aorticopulmonary septum/aorticopulmonary window

abnormal myocardium layer morphology ( J:18047 , J:35363 )

• all homozygotes display impaired differentiation or maturation of the ventricular cardiac myocytes (J:18047)

• spongy layer of the myocardium is generally thicker (J:35363)

abnormal myocardial trabeculae morphology ( J:35363 )

• 67% show attenuated trabeculae and contain an unusual, random branching pattern

trabecula carnea hypoplasia ( J:18047 )

• by E14.5, ventricular trabeculation is present but reduced and appears disorganized at the muscular septum

abnormal myocardium compact layer morphology ( J:18047 )

• by E14.5, homozygotes show absence of myocyte proliferation at the ventricular epicardial surface ("compact layer")

ventricular myocardium compact layer hypoplasia ( J:35363 )

• 94% exhibit a hypoplastic compact zone of the ventricular myocardium

abnormal ventricle papillary muscle morphology ( J:35363 )

• 56% exhibit dysmorphic papillary muscles

abnormal conotruncal ridge morphology ( J:35363 )

• 100% have abnormalities of conotruncal ridges ranging from mild deficiency of conotruncal tissue (6%) to complete absence of cushion tissue (66%)

persistent truncus arteriosus ( J:35363 )

• seen in 11% of homozygotes

abnormal atrioventricular cushion morphology ( J:35363 )

• exhibit a wide spectrum of atrioventricular cushion defects

• 67% show partial fusion of the atrioventricular cushions

failure of atrioventricular cushion closure ( J:35363 )

• complete lack of fusion of the superior and inferior atroioventricular cushions

double outlet right ventricle ( J:35363 )

• portion of embryos with shortened conotruncal ridges exhibit double outlet right ventricle (17%)

abnormal mitral valve morphology ( J:35363 )

• 17% show cleft mitral valve

mitral valve atresia ( J:18047 )

• by E14.4, 1 of 10 homozygotes displays mitral atresia

• no tricuspid atresia is observed

abnormal tricuspid valve morphology ( J:35363 )

• 17% show cleft tricuspid valve

abnormal heart left atrium morphology ( J:65904 )

• at E14.5, homozygotes exhibit normal atrial structure and function with no differences in overall position of heart and major vessels; however, the left atrium appears small

dilated heart right atrium ( J:18047 )

• at E14.5, 5 of 10 homozygotes display dilation of the right atrial chambers

complete atrioventricular septal defect ( J:35363 )

• 39% show a common atrioventricular canal

muscular ventricular septal defect ( J:18047 , J:35363 , J:65904 )

• at E14.5, homozygotes display a poorly developed ventricular septum (J:18047)

• by E14.5, 9 of 10 homozygotes display obvious ventricular septal defects at the septal-cushion fusion (J:18047)

• 94% exhibit a ventricular septal defect, with all defects being muscular (J:35363)

abnormal heart ventricle shape ( J:18047 , J:65904 )

• at E11.5 or later, homozygotes exhibit an uneven ventricular contour (J:18047)

• at E14.5, both ventricles exhibit a globular rather than elliptical shape, suggesting a dilated form of congestive heart failure (J:65904)

ventricular hypoplasia ( J:18047 )

• by E14.5, all (10 of 10) homozygotes show ventricular chamber hypoplasia

thin ventricular wall ( J:18047 , J:35363 )

• at E14.5, all (10 of 10) homozygotes exhibit a thinned ventricular wall (J:18047)

• at E13.5, the relatively thin-walled "atrial-like" phenotype of mutant ventricular muscle cells is shown to correlate with the aberrant, persistent expression of an atrial marker (J:18047)

dilated heart right ventricle ( J:18047 )

• at E14.5, some homozygotes display dilated right ventricles

abnormal pericardial cavity morphology ( J:18047 )

• by E14.5, most homozygotes show a prominent pericardial space

abnormal pericardium morphology ( J:18047 )

• at E11.5 and E12.5, homozygotes exhibit a loosely apposed pericardium; however, the pericardium appears relatively normal at E14.5

decreased cardiac output ( J:65904 )

decreased ventricle muscle contractility ( J:65904 )

• at E13.5 and E14.5, left ventricular area ejection fractions of mutant hearts average 14% vs 50% in wild-type hearts, indicating ventricular dysfunction

• at E14.5, depressed ejection fraction is related to thinned left ventricular wall and impaired shortening of the mutant myocardium

decreased heart rate ( J:65904 )

• at E13.5, homozygotes show normal AV synchrony and display heart rates comparable to those of wild-type mice; however, mutant heart rates are slightly decreased at E14.5

heart block ( J:65904 )

• at E14.5, 2 of 10 homozygotes display a complete heart block

atrioventricular block ( J:65904 )

• by E14.5, homozygotes with slightly reduced heart rates exhibit an intermittent partial AV block (not quantified)

congestive heart failure ( J:18047 , J:65904 )

• homozygotes appear to die in utero as a result of congestive heart failure (J:18047)

skin edema ( J:18047 )

• at E14.5, homozygotes display a dramatic subdermal edema, that is most prominent along the back and in the folds of skin around the eye

• however, most major organ systems, including the intestine, skin, kidney and eye, appear normal

decreased hepatocyte proliferation ( J:18047 )

• at E12.5, homozygotes exhibit a marked reduction in hepatocyte proliferation with substantial recovery to ~60% of wild-type values noted at E14.5

delayed hepatic development ( J:18047 )

small liver ( J:18047 )

• at E12.5, homozygotes display a liver mass that is ~30% of wild-type mice in the absence of morphological defects