Phenotypes Associated with This Genotype

Genotype
MGI:5825304

• Allelic Composition: Wdfy3^{tm1a(KOMP)Mbp}/Wdfy3^{tm1a(KOMP)Mbp}
• Genetic Background: C57BL/6N-Wdfy3^{tm1a(KOMP)Mbp}
• Cell Lines: DEPD00523_5_G11

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

Wdfy3^{tm1a(KOMP)Mbp}/Wdfy3^{tm1a(KOMP)Mbp} mice exhibit severe neurodevelopmental defects

mortality/aging

perinatal lethality, complete penetrance ( J:225200 )

• homozygotes die perinatally for unknown reasons

nervous system

abnormal neuronal migration ( J:225200 )

• analysis of cortical layer-specific markers Tbr1 (layer VI) and Ctip2 (layer V) revealed focal anomalies in the somatosensory and motor cortices at P0

abnormal forebrain development ( J:225200 )

• newborn pups exhibit more severe neurodevelopmental defects than Wdfy3^disc homozygotes

abnormal cerebral hemisphere morphology ( J:225200 )

• ~13% increase in overall cerebral size relative to wild-type controls

abnormal cerebral cortex morphology ( J:225200 )

• at E18.5, mice exhibit widespread focal cortical dysplasias that disrupt most cortical layers and invade the marginal zone

• focal cortical dysplasias occur at a higher frequency than in Wdfy3^disc homozygotes

abnormal neocortex morphology ( J:225200 )

• newborn brains show an even more drastic thinning and lengthening of the neocortex relative to that in Wdfy3^disc homozygotes

abnormal stratification in cerebral cortex ( J:225200 )

• abnormal cortical layer formation through intermingling of Ctip2+ neurons with Tbr1+ neurons in layer VI

thin cerebral cortex ( J:225200 )

• 16% reduction in neocortical thickness only in the most lateral position, with a trend towards thinning throughout the cortex

ectopic cortical neuron ( J:225200 )

• heterotopias are found in the somatosensory cortex and more dorsally in the motor area and can affect the hippocampus, unlike in Wdfy3^disc homozygotes where they are restricted to lateral aspects of the somatosensory area of the neocortex

cellular

abnormal neuronal migration ( J:225200 )

• analysis of cortical layer-specific markers Tbr1 (layer VI) and Ctip2 (layer V) revealed focal anomalies in the somatosensory and motor cortices at P0

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autistic disorder		DOID:12849	OMIM:209850 OMIM:300425 OMIM:300495 OMIM:300496 OMIM:300830 OMIM:300847 OMIM:300872 OMIM:607373 OMIM:608049 OMIM:608636 OMIM:609378 OMIM:610676 OMIM:610836 OMIM:610908 OMIM:611015 OMIM:611016 OMIM:611913 OMIM:612100 OMIM:613410 OMIM:613436 OMIM:615032 OMIM:615091	J:225200