Phenotypes Associated with This Genotype

Genotype
MGI:2656246

• Allelic Composition: Sema3a^tm1Mcf/Sema3a^tm1Mcf
• Genetic Background: involves: 129S4/SvJae

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

mortality/aging

lethality at weaning, incomplete penetrance ( J:35824 )

• 17% of homozygotes die at weaning

decreased survivor rate ( J:35824 )

• only 12% of homozygotes survive to adulthood

premature death ( J:35824 )

• ~1% of homozygotes are weaned but die over the next 3 months

postnatal lethality, incomplete penetrance ( J:35824 )

• 70% of homozygotes die within the first 3 days of life

• homozygotes that survive the first few days of life die over the next 3 weeks with fulminant right heart failure

prenatal lethality, incomplete penetrance ( J:35824 )

• homozygotes are born at slightly lower than predicted Mendelian ratios

behavior/neurological

decreased food intake ( J:35824 )

• newborn homozygotes contain less milk in their stomachs

weakness ( J:35824 )

• many homozygotes appear weak within 24 hrs after birth

abnormal posture ( J:35824 )

• surviving homozygotes have trouble maintaining an upright posture

growth/size/body

heart right ventricle hypertrophy ( J:35824 )

• at P10, the right ventricle is enlarged and its wall, normally thin by this age, is hypertrophied

• rare homozygotes that survive the first days of life die over the next 3 weeks displaying right ventricular hypertrophy, such that the right ventricle is equivalent to the left in thickness

• however, no obstruction of the right ventricular outflow or pulmonary valve is observed

decreased body size ( J:35824 )

• surviving homozygotes are smaller than wild-type littermates

cardiovascular system

heart right ventricle hypertrophy ( J:35824 )

• at P10, the right ventricle is enlarged and its wall, normally thin by this age, is hypertrophied

• rare homozygotes that survive the first days of life die over the next 3 weeks displaying right ventricular hypertrophy, such that the right ventricle is equivalent to the left in thickness

• however, no obstruction of the right ventricular outflow or pulmonary valve is observed

dilated heart right atrium ( J:35824 )

• at P10, homozygotes display massive dilatation of the right atrium

• the right atrium is generally filled with clot

skeleton

abnormal sternum morphology ( J:35824 )

• the sternum is thickened and displays an irregular border

asymmetric sternocostal joints ( J:35824 )

• homozygotes exhibit misalignment of the ribs with the sternum

split xiphoid process ( J:35824 )

• the xiphoid process may be split

abnormal rib morphology ( J:35824 )

• homozygotes display partial duplication of ribs

rib fusion ( J:35824 )

• homozygotes display rib fusions in the thoracic region

cervical vertebral fusion ( J:35824 )

• homozygotes exhibit fusion of cervical bones

nervous system

abnormal neuron differentiation ( J:127639 )

• axon density is increased 5.97-fold in hindlimbs and 3.74-fold in forelimbs compared to in wild-type mice

decreased brain size ( J:35824 )

• at P12, mutant brains are smaller than normal and comparable to those of P7 wild-type littermates

• all regions of the brain are reduced, in the absence of obvious histological abnormalities in the deep grey nuclei, cerebellum, or brainstem

abnormal cerebral cortex morphology ( J:35824 )

• at P12, the neuropil (a complex, feltlike net of axonal, dendritic, and glial arborizations located between neurons) is severely reduced

• all cortical layers are present, although less clearly demarcated

abnormal cerebral cortex pyramidal cell morphology ( J:35824 )

• at P12, many pyramidal neurons, esp. large pyramidal neurons of layer 5, are abnormally oriented, with processes pointing in random directions

thin cerebral cortex ( J:35824 )

• at P12, the thickness of the cerebral cortex is ~70% of wild-type and comparable to the thickness of the P7 wild-type cortex

abnormal sensory neuron innervation pattern ( J:35824 )

• some sensory axons project into inappropriate regions of the spinal cord, reaching the central canal and medial ventral cord

respiratory system

respiratory system phenotype ( J:35824 )

N • homozygotes display no evidence of pulmonary emboli or pulmonary artery hypertrophy, suggesting absence of pulmonary hypertension

cellular

abnormal neuron differentiation ( J:127639 )

• axon density is increased 5.97-fold in hindlimbs and 3.74-fold in forelimbs compared to in wild-type mice

muscle

heart right ventricle hypertrophy ( J:35824 )

• at P10, the right ventricle is enlarged and its wall, normally thin by this age, is hypertrophied

• rare homozygotes that survive the first days of life die over the next 3 weeks displaying right ventricular hypertrophy, such that the right ventricle is equivalent to the left in thickness

• however, no obstruction of the right ventricular outflow or pulmonary valve is observed

homeostasis/metabolism

abnormal atrial thrombosis ( J:35824 )

• at P10, the dilated right atrium is generally filled with clot