Phenotypes Associated with This Genotype

Genotype
MGI:4948448

• Allelic Composition: Celsr1^Crsh/Celsr1^Crsh
• Genetic Background: either: (involves: 101/H * C3H/HeH) or (involves: 101/H * BALB/c * C3H/HeH)

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

respiratory system

abnormal lung morphology ( J:159690 )

• at E14.5 and E18.5, mutant lungs show cytokeletal defects and disordered epithelial airways with no apparent disruption of adherens junctions

• however, apical-basal polarity remains intact

abnormal branching involved in lung morphogenesis ( J:159690 )

• at E14.5, a significant reduction in the number of epithelial branches is observed

• in explant cultures, mutant E11.5 lung endoderm denuded of mesenchyme responds to a chemoattractant FGF10 stimulus in terms of growth but is unable to undergo branching

• however, no significant changes in epithelial cell differentiation are observed in vivo at E18.5

• also, no significant changes in proliferation or apoptosis are observed at E11.5 or E14.5

abnormal lung saccule morphology ( J:159690 )

• at E18.5, mutant lungs show atypical saccular structure with no evidence of septation

thick lung-associated mesenchyme ( J:159690 )

• at E18.5, mutant lungs display a thickened interstitial mesenchyme

abnormal lung epithelium morphology ( J:159690 )

• at E14.5, the mutant lung epithelium is improperly aligned and shows a multilayered and/or disorganized morphology, unlike the single layer of uniformly aligned columnar epithelium seen in wild-type lungs

• at E14.5, mutant lung epithelial cells are highly disorganized and randomly orientated with either small or no lumina, and not readily distinguishable from surrounding mesenchyme by DAPI labeling

• Celsr1^Crsh airways appeared more severely affected than Vangl2^Lp airways

abnormal lung lobe morphology ( J:159690 )

• at E18.5, mutant lung lobes are visibly misshapen

small lung lobe ( J:159690 )

• at E18.5, mutant lung lobes are smaller than wild-type lobes

small lung ( J:159690 )

• at E18.5, mutant lungs are smaller than wild-type, likely due to the reduced width and number of airway lumina and increased compaction of the lung tissue

pulmonary hypoplasia ( J:159690 )

• at E18.5, mutant lungs are hypoplastic

abnormal respiratory conducting tube morphology ( J:159690 )

• at E14.5, most airway lumina are narrow or absent

• at E18.5, the number and width of mutant airways is severely reduced while the luminal space often contains cells

impaired branching involved in terminal bronchiole morphogenesis ( J:159690 )

• after 48 hrs in ex vivo culture, mutant E11.5 lungs are smaller with significantly fewer and larger terminal buds than wild-type lungs

• addition of the Rho activator CNF-1 to mutant lung explants partially rescues the branching defect, leading to a greater increase in bud numbers than in wild-type lungs (24% vs 16%, respectively)

dilated terminal bronchiole tube ( J:159690 )

• after 48 hrs in ex vivo culture, mutant E11.5 lungs display significantly enlarged terminal buds relative to wild-type lungs