Phenotypes associated with this allele

• Allele Symbol: Foxm1^tm1.1Rhc
• Allele Name: targeted mutation 1.1, Robert H Costa
• Allele ID: MGI:3522201
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Foxm1^tm1.1Rhc/Foxm1^tm1.1Rhc	B6.129X1-Foxm1^tm1.1Rhc	MGI:3710340
hm2	Foxm1^tm1.1Rhc/Foxm1^tm1.1Rhc	involves: 129X1/SvJ	MGI:3522669
hm3	Foxm1^tm1.1Rhc/Foxm1^tm1.1Rhc	involves: 129X1/SvJ * C57BL/6	MGI:3663791

Genotype
MGI:3710340

hm1

• Allelic Composition: Foxm1^tm1.1Rhc/Foxm1^tm1.1Rhc
• Genetic Background: B6.129X1-Foxm1^tm1.1Rhc

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

cardiovascular system

abnormal ventricle myocardium morphology ( J:119481 )

• E13.5-18.5 hearts exhibit thinning of the ventricular myocardium

abnormal fetal cardiomyocyte morphology ( J:119481 )

• severe accumulation of polyploid cardiomyocytes is seen in E13.5-18.5 heart tissues, including ventricular myocardium, interventricular septum, atrium, and heart trabeculae

• increase in the size of cardiomyocyte nuclei is noted at E15.5 and E18.5

decreased fetal cardiomyocyte number ( J:119481 )

• reduced number of cardiomyocytes at E13.5 and E18.5

increased fetal cardiomyocyte size ( J:119481 )

• enlarged cardiomyocytes are seen in the atrium and ventricle as early as E9.5

small heart ( J:119481 )

• 25% reduction in heart size at E15.5 but not at E13.5

ventricular hypoplasia ( J:119481 )

thick heart valve cusps ( J:119481 )

• 1.3-fold increase in thickness of heart valve leaflets at E13.5

thick mitral valve cusps ( J:119481 )

• thickening of atrioventricular (A/V) valves (mitral valve leaflets) at E13.5

decreased heart left ventricle size ( J:119481 )

• hearts show a 43% reduction in the thickness of the left ventricle at E13.5 and a 57% reduction at E15.5

dilated heart ventricle ( J:119481 )

• embryos display dilated heart ventricles

decreased fetal cardiomyocyte proliferation ( J:119481 )

• developing cardiomyocytes show diminished DNA replication and mitosis at E15.5

cellular

decreased fetal cardiomyocyte proliferation ( J:119481 )

• developing cardiomyocytes show diminished DNA replication and mitosis at E15.5

muscle

abnormal ventricle myocardium morphology ( J:119481 )

• E13.5-18.5 hearts exhibit thinning of the ventricular myocardium

decreased fetal cardiomyocyte proliferation ( J:119481 )

• developing cardiomyocytes show diminished DNA replication and mitosis at E15.5

Genotype
MGI:3522669

hm2

• Allelic Composition: Foxm1^tm1.1Rhc/Foxm1^tm1.1Rhc
• Genetic Background: involves: 129X1/SvJ

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:94883 )

• 75% were dead by E17.5 and all were dead by E18.5

cardiovascular system

abnormal liver sinusoid morphology ( J:94883 )

• disruption in the organization of liver sinusoids

abnormal hepatic vein morphology ( J:94883 )

• reduction in the number of large hepatic veins

increased myocardial fiber size ( J:94883 )

• enlarged polyploid embryonic cardiomyocytes were observed

hemorrhage ( J:94883 )

• at E17.5 embryos were transparent with hemorrhagic lesions

cellular

abnormal cell cycle ( J:94883 )

• decrease in BrdU incorporation without increase in apoptosis suggesting a block in mitosis; a decrease in expression of proteins required for cell cycle progression and cytokinesis was observed

homeostasis/metabolism

hydrops fetalis ( J:94883 )

• at E15.5 embryos exhibited a gelatin-like consistency; at E17.5 embryos exhibited edema

liver/biliary system

abnormal liver sinusoid morphology ( J:94883 )

• disruption in the organization of liver sinusoids

abnormal intrahepatic bile duct morphology ( J:94883 )

• abnormal development of the intrahepatic bile ducts

abnormal hepatoblast morphology ( J:94883 )

• presence of abnormal hepatoblast cells with enlarged polyploid nuclei

• decrease in BrdU incorporation without increase in apoptosis suggesting a block in mitosis; a decrease in expression of proteins required for cell cycle progression and cytokinesis was observed

decreased hepatoblast number ( J:94883 )

• reduced numbers of hepatoblasts; 75% reduction in the number of hepatoblasts compared to controls, but no decrease in overall size of liver suggesting a hypertrophy of remaining hepatoblasts

abnormal hepatic cord morphology ( J:94883 )

• disruption in the organization of hepatic cords

muscle

increased myocardial fiber size ( J:94883 )

• enlarged polyploid embryonic cardiomyocytes were observed

endocrine/exocrine glands

abnormal intrahepatic bile duct morphology ( J:94883 )

• abnormal development of the intrahepatic bile ducts

Genotype
MGI:3663791

hm3

• Allelic Composition: Foxm1^tm1.1Rhc/Foxm1^tm1.1Rhc
• Genetic Background: involves: 129X1/SvJ * C57BL/6

Foxm1^tm1.1Rhc/Foxm1^tm1.1Rhc embryonic lungs exhibit pulmonary artery hypertrophy

cardiovascular system

abnormal pulmonary artery morphology ( J:100263 )

• at E18.5, homozygotes exhibit severe hypertrophy of pulmonary arteries, associated with a 5-fold increase in arterial muscularity

aortic hypertrophy ( J:100263 )

• at E18.5, homozygotes display severe hypertrophy of vascular smooth muscle cells of the aorta

abnormal carotid artery morphology ( J:100263 )

• at E18.5, homozygotes display severe hypertrophy of vascular smooth muscle cells of the carotid artery

abnormal capillary morphology ( J:100263 )

• at E17.5, homozygotes show a significant reduction in the number of peripheral pulmonary capillaries

abnormal lung vasculature morphology ( J:100263 )

• at E15.5 and E17.5, homozygotes show a significant reduction in the number of large pulmonary vessels (arteries and veins with diameter = 25 um) and peripheral pulmonary capillaries, with no evidence of increased apoptosis

vascular smooth muscle hypertrophy ( J:100263 )

• at E18.5, homozygotes display severe hypertrophy of vascular smooth muscle cells of the pulmonary arteries, with abnormally large DAPI-stained nuclei

• many extrapulmonary arteries (e.g. the carotid artery and aorta) display severe hypertrophy of smooth muscle cells

• however, airway smooth muscle cells of E18.5 mutant pulmonary bronchi exhibit normal morphology

respiratory system

abnormal lung vasculature morphology ( J:100263 )

• at E15.5 and E17.5, homozygotes show a significant reduction in the number of large pulmonary vessels (arteries and veins with diameter = 25 um) and peripheral pulmonary capillaries, with no evidence of increased apoptosis

abnormal lung development ( J:100263 )

• homozygotes display defective lung development associated with aberrant expression of pulmonary genes involved in extracellular matrix remodeling, mesenchyme proliferation, and vasculogenesis

• however, mutant lung size, lobular architecture, and sacculation appear unaffected

decreased mesenchymal cell proliferation involved in lung development ( J:100263 )

• at E15.5, homozygotes display reduced proliferation of mesenchymal cells around the distal lung epithelium

muscle

vascular smooth muscle hypertrophy ( J:100263 )

• at E18.5, homozygotes display severe hypertrophy of vascular smooth muscle cells of the pulmonary arteries, with abnormally large DAPI-stained nuclei

• many extrapulmonary arteries (e.g. the carotid artery and aorta) display severe hypertrophy of smooth muscle cells

• however, airway smooth muscle cells of E18.5 mutant pulmonary bronchi exhibit normal morphology

cellular

decreased mesenchymal cell proliferation involved in lung development ( J:100263 )

• at E15.5, homozygotes display reduced proliferation of mesenchymal cells around the distal lung epithelium