Phenotypes Associated with This Genotype

Genotype
MGI:7489810

• Allelic Composition: Smc3^tm1.2Toshi/Smc3⁺
• Genetic Background: B6.Cg-Smc3^tm1.2Toshi

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

nervous system

nervous system phenotype ( J:242006 )

N • at 6 weeks of age, mice exhibit normal brain size, with no detectable gross abnormalities in brain anatomy

decreased CNS synapse formation ( J:242006 )

• mice exhibit impaired synapse maturation in cortical layer II/III, with higher numbers of immature synapses detected in the cerebral cortex

• at P21, Stat1 expression in the cortex is significantly higher than in wild-type controls

• inhibition of STAT1 expression partially rescues impaired synaptic formation

abnormal dendritic mushroom spine morphology ( J:242006 )

• at 8 weeks of age, the percentage of mushroom-type mature spines on apical dendrites of cortical layer II/III pyramidal neurons is lower than in wild-type controls

• moreover, at 6 weeks of age, the density of mushroom-type mature spines is significantly lower than in wild-type controls

decreased dendritic spine density ( J:242006 )

• at 6 weeks of age, the density of mushroom-type mature spines in layer II/III pyramidal neurons is significantly lower than in wild-type controls

increased dendritic spine length ( J:242006 )

• at 8 weeks of age, spine length of cortical layer II/III pyramidal neurons is significantly greater than in wild-type controls

abnormal dendritic thin spine morphology ( J:242006 )

• at 8 weeks of age, the percentage of thin- and filopodia-type immature spines on apical dendrites of cortical layer II/III pyramidal neurons is higher than in wild-type controls

• in contrast, the percentage of stubby spines is normal

abnormal pyramidal neuron dendrite morphology ( J:242006 )

• at 3 and 6 weeks of age, cortical layer II/III pyramidal neurons exhibit greater dendritic arbor complexity and dendrite length than in wild-type controls

abnormal postsynaptic density morphology ( J:242006 )

• expression of the excitatory postsynaptic protein postsynaptic density 95 (PSD-95) is reduced, with no significant change in the level of the excitatory presynaptic protein SLC17A7 (aka VGlut1)

• at 6 weeks of age, EM analysis showed significantly thinner and shorter postsynaptic densities than in wild-type controls

• after culture for 21 days, cortical neurons transfected with control siRNA show fewer numbers of PSD-95-positive puncta than wild-type neurons; however, lower PSD-95 density is partially rescued by Stat1 siRNA transfection

behavior/neurological

behavior/neurological phenotype ( J:242006 )

♂N • adult males (11-week-old or older) show no significant alterations in locomotion, nociception, social behavior, motor coordination, depression-like behavior or spatial memory

increased anxiety-related response ( J:242006 )

♂ • in the light/dark transition test, adult males exhibit a significantly longer latency to first entry into the light box, suggesting increased anxiety; however, distances traveled in the light or dark boxes, stay time in the light box, and the number of transitions are not altered

♂ • in the marble-burying test, adult males show more marble-burying behavior with no difference in total distance traveled

♂ • in the novelty-induced hypophagia test, adult males show a significantly longer latency to drink sweetened condensed milk in a novel, brightly lit cage; however, milk consumption in the novel cage is not significantly altered

hyperactivity ( J:242006 )

♂ • in a 24-h home cage-monitoring test, mice exhibit hyperactivity during the nighttime period

growth/size/body

growth/size/body region phenotype ( J:242006 )

N • at 1-8 weeks of age, both sexes exhibit normal body size, with no significant alterations in body weight relative to wild-type controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cornelia de Lange syndrome 3		DOID:0080507	OMIM:610759	J:242006