Phenotypes associated with this allele

• Allele Symbol: Foxf1^tm1Rhc
• Allele Name: targeted mutation 1, Robert H Costa
• Allele ID: MGI:2179135
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Foxf1^tm1Rhc/Foxf1^tm1Rhc	involves: 129P3/J * Black Swiss	MGI:3613576
ht2	Foxf1^tm1Rhc/Foxf1^+	involves: 129P3/J * Black Swiss	MGI:3613577
ht3	Foxf1^tm1Rhc/Foxf1^+	involves: 129P3/J * Black Swiss * CD-1	MGI:4888586

Genotype
MGI:3613576

hm1

• Allelic Composition: Foxf1^tm1Rhc/Foxf1^tm1Rhc
• Genetic Background: involves: 129P3/J * Black Swiss

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:70364 )

• no embryos are present at E15.5

Genotype
MGI:3613577

ht2

• Allelic Composition: Foxf1^tm1Rhc/Foxf1⁺
• Genetic Background: involves: 129P3/J * Black Swiss

mortality/aging

premature death ( J:70364 )

• 5% of surviving pups die within 6 weeks of birth; the remaining 40% with near wild-type levels of Foxf1a expression have normal lifespans

neonatal lethality, incomplete penetrance ( J:70364 )

• 55% of newborns with lower than expected levels of Foxf1a expression die of severe lung hemorrhage within several hours of birth

respiratory system

lung hemorrhage ( J:70364 )

• at P0 but not E18 in mice that exhibit neonatal lethality, severe lung hemorrhage is seen

• red blood cells are detected in peripheral airspaces and in bronchioles

• lung hemorrhage is coincident with disruption of the mesenchymal-epithelial cell interfaces in the alveolar and bronchiolar regions

abnormal lung morphology ( J:70364 )

• apoptotic cells are seen throughout the lung parenchyma, in smooth muscle cells underlying the bronchiolar epithelium, and in arterial smooth muscle cells in mice that exhibit pulmonary hemorrhage

abnormal lung vasculature morphology ( J:70364 )

• impaired development of the alveolar capillaries is observed at birth

impaired lung alveolus development ( J:70364 )

• in mice that exhibit neonatal lethality, sacculation of the lung periphery is reduced indicating a failure to undergo differentiation of the terminal airspaces; a less severe defect in septation of the lung periphery is seen in surviving mice

abnormal lung saccule morphology ( J:70364 )

• reduced sacculation of the lung periphery in mice that exhibit neonatal lethality

respiratory distress ( J:70364 )

• neonates that die shortly after birth have breathing difficulties

abnormal surfactant secretion ( J:70364 )

• reduced surfactant protein B (SP-B) expression in mice that exhibit neonatal lethality

cardiovascular system

abnormal lung vasculature morphology ( J:70364 )

• impaired development of the alveolar capillaries is observed at birth

lung hemorrhage ( J:70364 )

• at P0 but not E18 in mice that exhibit neonatal lethality, severe lung hemorrhage is seen

• red blood cells are detected in peripheral airspaces and in bronchioles

• lung hemorrhage is coincident with disruption of the mesenchymal-epithelial cell interfaces in the alveolar and bronchiolar regions

Genotype
MGI:4888586

ht3

• Allelic Composition: Foxf1^tm1Rhc/Foxf1⁺
• Genetic Background: involves: 129P3/J * Black Swiss * CD-1

mortality/aging

neonatal lethality, complete penetrance ( J:76411 )

• neonatal lethality correlates with severe fusion of the right lung lobes and low pulmonary FoxF1a mRNA levels

• a mild fusion between the accessory and caudal lobes is insufficient to cause lethality

respiratory system

abnormal lung vasculature morphology ( J:76411 )

• fusion of embryonic lung lobes is accompanied by misorientation and fusion of the large major pulmonary vessels

abnormal lung development ( J:76411 )

• altered lung-bud orientation and reduced branching morphogenesis is noted at E10.5-E11; a caudal and lateral shift in the orientation of the accessory lobe, and a lateral shift in the middle and cranial lobe positions are commonly observed

• a range of fusion defects in the right pulmonary lobes are noted at E12-E13

• by E18, most embryonic lungs display fusion of the accessory and caudal lobes and abnormal orientation of the accessory lobe

• at E18, ~13% of embryonic lungs exhibit more severe malformations in which the cranial, caudal, and middle lobes are fused

abnormal lung bud morphology ( J:76411 )

• at E11, impaired lung-bud formation is associated with reduced mesenchymal-epithelial interfaces

fused right lung lobes ( J:76411 )

• ~35-50% of heterozygous embryonic and newborn lungs exhibit severe lung fusions in the right lobes; however, only one severely fused lung is noted several days postnatally

• most adult heterozygotes display distinct cranial, middle, and caudal lobes and lack the severely fused lobes seen in embryos

• most adult heterozygotes show a mild fusion between the caudal and accessory right lobes resulting in a lateral shift in the position of the accessory lobe

cardiovascular system

abnormal lung vasculature morphology ( J:76411 )

• fusion of embryonic lung lobes is accompanied by misorientation and fusion of the large major pulmonary vessels