Phenotypes Associated with This Genotype

Genotype
MGI:2175179

• Allelic Composition: Ntf3^tm1Par/Ntf3^tm1Par
• Genetic Background: involves: 129S1/Sv

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

mortality/aging

perinatal lethality, incomplete penetrance ( J:44286 , J:67562 )

• about 10% die at birth (J:67562)

postnatal lethality, complete penetrance ( J:67562 )

• 80% die within 24-48 hours and a few survive up to 16 days

growth/size/body

enlarged heart ( J:35639 )

• enlarged and globular heart

cardiac hypertrophy ( J:35639 )

• medial hypertrophy

decreased body weight ( J:67562 )

• rare postnatal survivors fail to thrive and body weight is 25-50% that of controls, however weight is normal at birth

nervous system

abnormal somatic nervous system morphology ( J:44286 )

decreased sensory neuron number ( J:44286 , J:60927 )

• reduction of neurons in sensory ganglia, however motor neuron numbers are normal (J:44286)

• sensory neuron loss occurs from E12.5 to P0.5 (J:44286)

small geniculate ganglion ( J:44286 )

• 47% reduction of neurons in the geniculate ganglion

small petrosal ganglion ( J:44286 )

• 44% reduction of neurons in the nodose/petrosal ganglion

small trigeminal ganglion ( J:44286 , J:60927 )

• 68% reduction of neurons in the trigeminal ganglion (J:44286)

• 65% reduction of trigeminal ganglion neurons at P0 (J:60927)

small nodose ganglion ( J:44286 )

• 44% reduction of neurons in the nodose/petrosal ganglion

abnormal dorsal root ganglion morphology ( J:154926 )

• all large-diameter TrkC (Ntrk3)+ neurons are lost unlike in wild-type mice

abnormal proprioceptive neuron morphology ( J:67562 )

• loss of proprioceptive neurons as observe no Ia afferent projections to the motor neurons in spinal cords at any axial level examined at E15.5

small L4 dorsal root ganglion ( J:44286 )

• 79% reduction of neurons in the L4 dorsal root ganglion

small dorsal root ganglion ( J:60927 )

• 36% and 78% reduction of dorsal root ganglion neurons at E13 and P0, respectively

decreased spinal cord size ( J:67562 )

• reduction of spinal cord diamater

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:67562 )

• exhibit radically abnormal movements

abnormal posture ( J:67562 )

cardiovascular system

abnormal cardiovascular system morphology ( J:35639 )

• homozygotes display a range of heart defects that are seen in various combinations

abnormal blood vessel morphology ( J:67562 )

dilated pulmonary artery ( J:35639 )

• 2 of 15 homozgyotes with large ventricular septal defects and cardiac outflow tract abnormalities exhibit dilation of the pulmonary artery

premature closure of the ductus arteriosus ( J:35639 )

• premature closure of the ductus arteriosus secondary to medial hypertrophy is seen in utero or immediately after birth in all homozygotes

vascular smooth muscle hypotrophy ( J:35639 )

• 50% exhibit marked attenuation of the smooth muscle layer of the pulmonary vein

abnormal pulmonary vein morphology ( J:35639 )

• 50% exhibit marked attenuation of the smooth muscle layer of the pulmonary vein

abnormal heart morphology ( J:67562 )

abnormal atrium myocardial trabeculae morphology ( J:35639 )

• atria displays decreased trabeculations

atrium myocardium hypoplasia ( J:35639 )

• myocyte thinning of the atrial wall

persistent truncus arteriosus ( J:35639 )

• develops in 1 of 15 homozygotes

abnormal heart development ( J:35639 )

• at E9.5, exhibit developmental anomalies of the great vessels, including delay in the primitive myofibril organization of the truncus arteriosis, hypoplasia of the sinus venosus and atrial enlargement

abnormal sinus venosus morphology ( J:35639 )

• 50% exhibit defects in the sinus venosus

sinus venosus hypoplasia ( J:35639 )

• at E9.5, detect hypoplasia of the sinus venosus

overriding aortic valve ( J:35639 )

• 2 of 15 homozgyotes with large ventricular septal defects and cardiac outflow tract abnormalities exhibit an overriding aorta

ostium secundum atrial septal defect ( J:35639 )

• large secundum atrial septal defects

dilated heart atrium ( J:35639 )

• both atria are dilated

enlarged heart ( J:35639 )

• enlarged and globular heart

cardiac hypertrophy ( J:35639 )

• medial hypertrophy

abnormal heart valve morphology ( J:35639 )

• homozygotes exhibit variable valvular abnormalities

abnormal atrioventricular valve morphology ( J:35639 )

• dilation of the atrioventricular annuli is the most consistent defect observed

thick mitral valve cusps ( J:35639 )

• 50% exhibit thickened leaflets of the aortic valve or mitral valve

abnormal semilunar valve morphology ( J:35639 )

• 5 of 15 show pulmonic stenosis with abnormally thickened semilunar valve

abnormal heart ventricle morphology ( J:35639 )

perimembraneous ventricular septal defect ( J:35639 )

• 3 of 15 display a ventricular spetal defect in the region of the membranous septum

abnormal heart left ventricle size ( J:35639 )

• left ventricular size is variable

abnormal heart ventricle outflow tract morphology ( J:35639 )

• 2 of 15 homozygotes with large ventricular septal defects also have cardiac outflow tract abnormalities

thick aortic valve cusps ( J:35639 )

• 50% exhibit thickened leaflets of the aortic valve or mitral valve

heart right ventricle outflow tract stenosis ( J:35639 )

• 3 of 15 show subpulmonic stenosis

pulmonary valve stenosis ( J:35639 )

• 5 of 15 show pulmonic stenosis with abnormally thickened semilunar valve

dilated heart right ventricle ( J:35639 )

aneurysm ( J:35639 )

• 50% exhibit aneurismal dilation

pulmonary alveolar hemorrhage ( J:35639 )

• intra-alveolar hemorrhage

decreased heart rate ( J:35639 )

• resting heart rate is about 250 beats/min compared to 350 beats/min in wild-type at 8 hours after birth

• display a sensitivity to transthoracic pressure during echocardiography imaging, with significant bradycardia that recovers immediately on removal of the imaging catheter, which may reflect an abnormal autonomic tone

homeostasis/metabolism

pulmonary edema ( J:35639 )

• seen in all mutants

muscle

vascular smooth muscle hypotrophy ( J:35639 )

• 50% exhibit marked attenuation of the smooth muscle layer of the pulmonary vein

abnormal atrium myocardial trabeculae morphology ( J:35639 )

• atria displays decreased trabeculations

atrium myocardium hypoplasia ( J:35639 )

• myocyte thinning of the atrial wall

respiratory system

pulmonary alveolar hemorrhage ( J:35639 )

• intra-alveolar hemorrhage

pulmonary edema ( J:35639 )

• seen in all mutants

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
atrial heart septal defect 1		DOID:0110106	OMIM:108800	J:35639
tetralogy of Fallot		DOID:6419	OMIM:187500	J:35639