Phenotypes Associated with This Genotype

Genotype
MGI:5294810

• Allelic Composition: Cdh5^{tm3(Cdh5/Ctnna1)Dvst}/Cdh5^{tm3(Cdh5/Ctnna1)Dvst}
• Genetic Background: B6.Cg-Cdh5^{tm3(Cdh5/Ctnna1)Dvst}

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

cardiovascular system

cardiovascular system phenotype ( J:213676 )

N • at E10.5, homozygotes display no gross abnormalities in angiogenesis, as shown by PECAM-1 whole-mount immunostaining

N • at E13.5 and E14.5, analysis of the area covered by endomucin-positive vessels in fetal skin revealed no defects in angiogenesis

N • no heart defects in cushion formation are detected at E11.0

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:213676 )

• homozygotes die late during fetal development

• only 13 of 18 homozygotes are viable at E16.5, with no homozygotes identified at P21

embryonic lethality during organogenesis, incomplete penetrance ( J:213676 )

• homozygotes start dying around E13.5

• however, homozygotes are viable and phenotypically normal at E9.5

embryonic lethality, complete penetrance ( J:177191 )

• Background Sensitivity: 100% unlike on a mixed background

hematopoietic system

abnormal definitive hematopoiesis ( J:213676 )

• at E13.5, homozygotes display a reduced ratio of hematopoietic to hepatoblastic cells in fetal liver, indicating impaired fetal liver hematopoiesis

• however, at E10.5, endothelial to hematopoietic transition in the dorsal aorta is normal

abnormal common myeloid progenitor cell morphology ( J:213676 )

• at E13.5, the frequency of clonogenic progenitor cells (CFUs) is significantly increased in fetal blood and reduced in fetal liver

• however, the relative abundance of different progenitor types is not changed in fetal liver

increased hematopoietic precursor cell number ( J:213676 )

• at E13.5, homozygotes display a significant increase of c-Kit-positive, lineage marker-negative (c-Kit+ lin-) hematopoietic progenitors in fetal circulation

abnormal hematopoietic stem cell physiology ( J:213676 )

• at E13.5, hematopoietic stem and progenitor cells (HSPCs) accumulate in the fetal circulation suggesting that their entry into the fetal liver is blocked

• however, no defects in the generation of HSPCs from hemogenic endothelium or their differentiation into multiple hematopoietic lineages are observed

homeostasis/metabolism

lymphedema ( J:213676 )

• starting at E13.5, homozygotes display edema formation of variable severity as a result of disturbed lymphatic vessel development

• 64% of mutant fetuses at E13.5 and ~80% at E14.5 exhibit visible edema

immune system

abnormal lymphatic vessel morphology ( J:213676 )

• starting at E13.5, homozygotes display progressive disruption of lymphatic vessel integrity in fetal skin

• although the first or initial Prox1+ LECs are able to leave the cardinal vein and migrate to the site of the first lymphatic vessel formation, morphogenesis of the first large lymphatic vessels, pTD (primordial thoracic duct) and PLLV (peripheral longitudinal lymphatic vessel), is impaired

• at E12.0, lumenization pTD and PLLV is severely impaired

• pTD shows a discontinuous lumen with multiple constrictions and appears fragmented while abnormal structures of lymphatic vessels are formed from the PLLV

abnormal lymphatic vessel endothelium morphology ( J:213676 )

• at E13.5, lymphatic endothelial cells (LECs) are present but do not form a branched network as in controls

• at E14.5, only islands of disconnected LECs are detectable, unlike in control fetuses where further maturation of the lymphatic vascular plexus is observed

• however, at 13.5 and E14.5, the blood vasculature and VE-cadherin staining of lymphatic junctions is normal

liver/biliary system

small liver ( J:213676 )

• at E14.5, all homozygotes show a variable reduction in fetal liver size

• in 50% of homozygotes, average fetal liver weight/cellularity is down to 20%-50% of wild-type controls

decreased liver weight ( J:213676 )

• at E13.5 and E14.5, average fetal liver weight is significantly reduced

liver hypoplasia ( J:213676 )

• at E13.5 and E14.5, average fetal liver cellularity is significantly reduced