Phenotypes associated with this allele

• Allele Symbol: Arhgef18^em2Cya
• Allele Name: endonuclease-mediated mutation 2, Cyagen Biosciences
• Allele ID: MGI:7582406
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Arhgef18^em2Cya/Arhgef18^em2Cya Nkx2-5^em1(cre)Smoc/Nkx2-5^+	involves: C57BL/6JCya * C57BL/6JSmoc	MGI:8318803
cn2	Arhgef18^em2Cya/Arhgef18^+ Nkx2-5^em1(cre)Smoc/Nkx2-5^+	involves: C57BL/6JCya * C57BL/6JSmoc	MGI:8318804

Genotype
MGI:8318803

cn1

• Allelic Composition: Arhgef18^em2Cya/Arhgef18^em2Cya; Nkx2-5^em1(cre)Smoc/Nkx2-5⁺
• Genetic Background: involves: C57BL/6JCya * C57BL/6JSmoc

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

growth/size/body

decreased body weight ( J:379569 )

• mice exhibit a significantly lower body weight than control mice at all time points between 3 and 12 weeks of age

slow postnatal weight gain ( J:379569 )

• mice show significant deceleration of body weight growth beginning at 3 weeks of age

cardiovascular system

abnormal myocardium layer morphology ( J:379569 )

• at 4 weeks of age, mice exhibit skeletal reorganization of the myocardium with significantly reduced mRNA expression of cytoskeleton-related genes (vinculin, alpha/beta-tubulin, and alpha-actinin) and decreased levels of cytoskeletal proteins (vinculin, alpha/beta-tubulin, and TNNT2/cTNT) in myocardial tissue relative to controls

• mRNA expression of cell polarity-related genes (Pard3 and Scrib) and expression of the polarity proteins SCRIB and CRB2 are significantly lower at 4 weeks, suggesting myocardial tissue polarity defects

abnormal myocardial fiber morphology ( J:379569 )

• at 4 weeks of age, cardiomyocytes show a significant decrease in the immunofluorescence intensity of cytoskeletal proteins (vinculin, alpha/beta-tubulin, TNNT2/cTNT, and alpha-actinin), suggesting cardiomyocyte cytoskeletal rearrangements

• moreover, cardiomyocytes show a significant decrease in the fluorescence intensity of the polarity protein PARD3, consistent with disruption of myocardial tissue polarity

decreased heart left ventricle anterior wall thickness ( J:379569 )

• mice show a significant decrease in LV anterior wall thickness at end systole starting from 4- to 24 weeks of age

dilated heart left ventricle ( J:379569 )

• mice show a significant increase in both LV inner diameter and LV volume at end systole starting from 4- to 24 weeks of age

increased heart ventricle size ( J:379569 )

• at 4 weeks of age, mice exhibit biventricular enlargement with significantly larger bilateral ventricular volumes than controls

increased heart left ventricle size ( J:379569 )

• at 4 weeks of age

increased heart right ventricle size ( J:379569 )

• at 4 weeks of age

dilated cardiomyopathy ( J:379569 )

• mice develop dilated cardiomyopathy starting at 4 weeks of age

decreased heart left ventricle muscle contractility ( J:379569 )

• after 4 weeks of age, mice show a progressive decline in left ventricular (LV) systolic function, as evidenced by a significant reduction in LV ejection fraction and fraction shortening, accompanied by an increase in both LV inner diameter and LV volume at end systole as well as a decrease in LV anterior wall thickness at end systole; differences become increasingly pronounced with advancing age

• mRNA expression levels of Nppa (natriuretic peptide type A) and Nppb (natriuretic peptide type B) are significantly increased within ventricular muscle tissue at 4 weeks of age, consistent with early cardiac dysfunction

muscle

abnormal myocardium layer morphology ( J:379569 )

• at 4 weeks of age, mice exhibit skeletal reorganization of the myocardium with significantly reduced mRNA expression of cytoskeleton-related genes (vinculin, alpha/beta-tubulin, and alpha-actinin) and decreased levels of cytoskeletal proteins (vinculin, alpha/beta-tubulin, and TNNT2/cTNT) in myocardial tissue relative to controls

• mRNA expression of cell polarity-related genes (Pard3 and Scrib) and expression of the polarity proteins SCRIB and CRB2 are significantly lower at 4 weeks, suggesting myocardial tissue polarity defects

abnormal myocardial fiber morphology ( J:379569 )

• at 4 weeks of age, cardiomyocytes show a significant decrease in the immunofluorescence intensity of cytoskeletal proteins (vinculin, alpha/beta-tubulin, TNNT2/cTNT, and alpha-actinin), suggesting cardiomyocyte cytoskeletal rearrangements

• moreover, cardiomyocytes show a significant decrease in the fluorescence intensity of the polarity protein PARD3, consistent with disruption of myocardial tissue polarity

dilated cardiomyopathy ( J:379569 )

• mice develop dilated cardiomyopathy starting at 4 weeks of age

decreased heart left ventricle muscle contractility ( J:379569 )

• after 4 weeks of age, mice show a progressive decline in left ventricular (LV) systolic function, as evidenced by a significant reduction in LV ejection fraction and fraction shortening, accompanied by an increase in both LV inner diameter and LV volume at end systole as well as a decrease in LV anterior wall thickness at end systole; differences become increasingly pronounced with advancing age

• mRNA expression levels of Nppa (natriuretic peptide type A) and Nppb (natriuretic peptide type B) are significantly increased within ventricular muscle tissue at 4 weeks of age, consistent with early cardiac dysfunction

cellular

abnormal cell cytoskeleton morphology ( J:379569 )

• at 4 weeks of age, cardiomyocytes show cytoskeletal rearrangements, as indicated by reduced expression of cytoskeleton-related genes and proteins

mortality/aging

mortality/aging ( J:379569 )

N • mice exhibit no significant differences in survival curves relative to controls

Genotype
MGI:8318804

cn2

• Allelic Composition: Arhgef18^em2Cya/Arhgef18⁺; Nkx2-5^em1(cre)Smoc/Nkx2-5⁺
• Genetic Background: involves: C57BL/6JCya * C57BL/6JSmoc

cardiovascular system

cardiovascular system phenotype ( J:379569 )

N • short-axis M-mode ultrasound images show no significant changes in cardiac function or heart ventricle size relative to controls at 2 or 4 weeks of age

abnormal myocardium layer morphology ( J:379569 )

• at 4 weeks of age, mice exhibit significantly reduced mRNA expression of cytoskeleton-related genes (vinculin, alpha/beta-tubulin) and decreased levels of cytoskeletal proteins (vinculin, alpha/beta-tubulin, and TNNT2/cTNT) in myocardial tissue relative to controls

• mRNA expression of cell polarity-related genes (Pard3 and Scrib) and expression of the polarity protein SCRIB are significantly lower at 4 weeks, suggesting myocardial tissue polarity defects

abnormal myocardial fiber morphology ( J:379569 )

• at 4 weeks of age, cardiomyocytes show a significant decrease in the immunofluorescence intensity of cytoskeletal proteins (vinculin, alpha/beta-tubulin, TNNT2/cTNT, and alpha-actinin), suggesting cardiomyocyte cytoskeletal rearrangements

• moreover, cardiomyocytes show a significant decrease in fluorescence intensity of the polarity protein PARD3, consistent with disruption of myocardial tissue polarity

muscle

abnormal myocardium layer morphology ( J:379569 )

• at 4 weeks of age, mice exhibit significantly reduced mRNA expression of cytoskeleton-related genes (vinculin, alpha/beta-tubulin) and decreased levels of cytoskeletal proteins (vinculin, alpha/beta-tubulin, and TNNT2/cTNT) in myocardial tissue relative to controls

• mRNA expression of cell polarity-related genes (Pard3 and Scrib) and expression of the polarity protein SCRIB are significantly lower at 4 weeks, suggesting myocardial tissue polarity defects

abnormal myocardial fiber morphology ( J:379569 )

• at 4 weeks of age, cardiomyocytes show a significant decrease in the immunofluorescence intensity of cytoskeletal proteins (vinculin, alpha/beta-tubulin, TNNT2/cTNT, and alpha-actinin), suggesting cardiomyocyte cytoskeletal rearrangements

• moreover, cardiomyocytes show a significant decrease in fluorescence intensity of the polarity protein PARD3, consistent with disruption of myocardial tissue polarity

cellular

abnormal cell cytoskeleton morphology ( J:379569 )

• at 4 weeks of age, cardiomyocytes show cytoskeletal rearrangements, as indicated by reduced expression of cytoskeleton-related genes and proteins

growth/size/body

growth/size/body region phenotype ( J:379569 )

N • mice exhibit normal body weight gain from 1- to 12 weeks of age relative to controls

mortality/aging

mortality/aging ( J:379569 )

N • mice exhibit no significant differences in survival curves relative to controls