Phenotypes Associated with This Genotype

Genotype
MGI:3042302

• Allelic Composition: Phc1^tm1Os/Phc1^tm1Os
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

Phc1^tm1Os/Phc1^tm1Os hearts show abnormal cardiac looping at E9.5

muscle

heart right ventricle hypertrophy ( J:43764 )

mortality/aging

perinatal lethality, complete penetrance ( J:43764 )

• expected ratio of homozygotes through E17.5

• reduced proportion of homozygotes at birth (15 out of 146 newborns)

• 2 born dead and 7 cyanotic at birth

• remaining homozygotes became cyanotic and died within a few hours of birth

cardiovascular system

pulmonary trunk hypoplasia ( J:43764 )

• hypoplasia of the pulmonary trunk

abnormal cardiovascular development ( J:78065 )

abnormal cardiac outflow tract development ( J:78065 )

• truncus arteriosus and bulbus cordis are extremely deformed

abnormal heart morphology ( J:43764 )

• about 1/3 of hearts display characteristics of tetralogy of Fallot

heart right ventricle hypertrophy ( J:43764 )

abnormal heart looping ( J:78065 )

• incomplete looping of the heart tube seen at E9.5

abnormal bulbus cordis morphology ( J:78065 )

• bulbus cordis is extremely deformed

overriding aortic valve ( J:43764 )

• aorta straddles a large ventricular septal defect

ventricular septal defect ( J:43764 )

abnormal semilunar valve morphology ( J:43764 )

aortic valve stenosis ( J:43764 )

abnormal heart right ventricle outflow tract morphology ( J:43764 )

• stenosis of the right ventricular infundibulum

pulmonary valve stenosis ( J:43764 )

thin ventricular wall ( J:43764 )

• both ventricles have a thin myocardium

dilated heart ventricle ( J:43764 )

• both ventricles are dilated

craniofacial

small occipital bone ( J:43764 )

• reduced occipital bone

palatal shelves fail to meet at midline ( J:43764 )

cleft hard palate ( J:43764 )

• bilateral cleft of hard palate seen in 10 of 14 homozygotes

bilateral cleft palate ( J:43764 )

endocrine/exocrine glands

parathyroid hypoplasia ( J:43764 )

decreased thymus weight ( J:43764 )

• about half normal size

growth/size/body

heart right ventricle hypertrophy ( J:43764 )

palatal shelves fail to meet at midline ( J:43764 )

cleft hard palate ( J:43764 )

• bilateral cleft of hard palate seen in 10 of 14 homozygotes

bilateral cleft palate ( J:43764 )

decreased body size ( J:43764 )

• homozygotes are smaller in size than normal littermates

hematopoietic system

decreased thymus weight ( J:43764 )

• about half normal size

abnormal B cell differentiation ( J:75707 )

• B cells are reduced resulting in an overall reduction of lymphoid lineages in peripheral blood

extramedullary hematopoiesis ( J:75707 )

• nucleated cells in the spleen are reduced to about 12.5% of normal

• at E12.5 the numbers of spleen precursor cells are significantly reduced

impaired hematopoiesis ( J:75707 )

• hematopoietic cell expansion normal until around E14.5 after which it declines

abnormal hematopoietic stem cell morphology ( J:75707 )

• hematopoietic stem cells are unable to enhance survival by repopulating lethally irradiated recipients

decreased spleen weight ( J:43764 )

• about half normal size

immune system

decreased thymus weight ( J:43764 )

• about half normal size

abnormal B cell differentiation ( J:75707 )

• B cells are reduced resulting in an overall reduction of lymphoid lineages in peripheral blood

decreased spleen weight ( J:43764 )

• about half normal size

skeleton

small occipital bone ( J:43764 )

• reduced occipital bone

abnormal sternum morphology ( J:43764 )

• sternal defects including loss of the fifth ossification point

abnormal vertebrae morphology ( J:43764 )

cervical vertebral fusion ( J:43764 )

• C1 and C2 are frequently fused

cervical vertebral transformation ( J:43764 )

• C7 takes the form of T1

lumbar vertebral transformation ( J:43764 )

• L6 takes the form of S1

vision/eye

abnormal optic cup morphology ( J:43764 )

• variable abnormalities include the absence or hypoplasia of the optic cup, with the abnormalities often more severe in the right optic cup than the left optic cup

• when present, abnormal rotations of the optic cups are sometimes seen

• the optic cups of the 12.5 d.p.c. embryos are significantly smaller in the homozygotes

digestive/alimentary system

palatal shelves fail to meet at midline ( J:43764 )

cleft hard palate ( J:43764 )

• bilateral cleft of hard palate seen in 10 of 14 homozygotes

bilateral cleft palate ( J:43764 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
tetralogy of Fallot		DOID:6419	OMIM:187500	J:43764