Phenotypes Associated with This Genotype

Genotype
MGI:5824267

• Allelic Composition: Wt1^tm1.1Ndha/Wt1^tm1.1Ndha; Tg(Gata4*G2-cre)#Roja/0
• Genetic Background: involves: 129P2/OlaHsd

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:229936 , J:238024 )

• embryonic lethality around E15.5 (J:229936)

• fewer than the expected number of mutants are obtained at E15.5 (J:238024)

cardiovascular system

thin ventricle myocardium compact layer ( J:229936 )

• embryos show a thin ventricular compact myocardium

• however, the epicardium remains intact

abnormal coronary vessel morphology ( J:229936 )

• impaired development of coronary vasculature

• embryos develop tortuous and sinusoidal irregular vessels that fail to progress transmurally and do not complete ventricular myocardium invasion

• normal coronary arteries are missing

• mutant N1ICD+ coronary endothelium does not form normal transmural coronary blood vessels, failing to connect to the deeper vascular elements of the developing coronary vasculature

embryo

abnormal intermediate mesoderm morphology ( J:238024 )

• persistence of the intermediate mesoderm of the nephric ridges into the pleuroperitoneal folds

abnormal mesenchyme morphology ( J:238024 )

• fewer mesenchymal cells are present between the coelomic epithelium and the hepatoblasts at E10.5

• the mesenchymal cells of the posthepatic mesenchymal plate are located more medially, not in the lateral tips of the liver lobes, indicating that these cells cannot migrate towards the pleuroperitoneal folds

• some E12.5 embryos show strong reduction of the posthepatic mesenchymal plate size

muscle

thin ventricle myocardium compact layer ( J:229936 )

• embryos show a thin ventricular compact myocardium

• however, the epicardium remains intact

abnormal diaphragm development ( J:238024 )

• about 80% of E13.5 or older embryos show abnormal diaphragmatic development

• the closure of the pleural cavity by growth of the septum transversum/pleuroperitoneal folds crescent is delayed

diaphragmatic hernia ( J:238024 )

• about 80% of mice develop Bochdaleks congenital diaphragmatic hernia, most frequently located in the left side

• diaphragmatic defect becomes apparent by E13.5, with 19 of 23 embryos showing diaphragmatic defects by E13.5 or older

• 3 of 23 embryos show thin, membranous diaphragm in the left side and 16 of 23 show a wide defect in the diaphragm, frequently with herniation of the liver into the left pleural cavity and hypoplasia of the left lung

• treatment of pregnant females with retinoic acid partially rescues diaphragm defects

respiratory system

abnormal pleural cavity morphology ( J:238024 )

• the closure of the pleural cavity by growth of the septum transversum/pleuroperitoneal folds crescent is delayed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital diaphragmatic hernia		DOID:3827	OMIM:142340 OMIM:222400 OMIM:610187	J:238024