Phenotypes Associated with This Genotype

Genotype
MGI:4420313

• Allelic Composition: Gja1^tm1Dlg/Gja1^tm1Dlg; Tg(GFAP-cre)1Kdmc/0
• Genetic Background: involves: 129S7/SvEvBrd * C3H * C57BL/6 * C57BL/6J

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

mortality/aging

premature death ( J:156098 )

• Shuffler mice develop motor defects and die apparently due to malnutrition

nervous system

abnormal radial glial cell morphology ( J:156098 )

• at P2, radial glial cells in Shuffler mice that stretch across the cortical layers are not as prominent or organized as in wild-type mice

abnormal brain morphology ( J:156098 )

• Background Sensitivity: mice further backcrossed to 129S/SvEv exhibit behavioral and neurological defects identified as the Shuffler phenotype unlike mice further backcrossed to C57BL/6J mice

• the relationship between the mesencephalon and the dorsal telencephalon is altered in Shuffler mice compared to in wild-type mice

abnormal cortical ventricular zone morphology ( J:156098 )

• at P2, the Shuffler ventricular zone is virtually cell-free, particularly in the lateral and medial cortex, unlike in wild-type mice

• however, the ventricular zone is normal at P10

enlarged brain ventricles ( J:156098 )

• Shuffler mice exhibit enlarged ventricles compared with wild-type mice

enlarged lateral ventricles ( J:156098 )

• sporadically in Shuffler mice

abnormal hippocampus morphology ( J:156098 )

• at P10, neuronal lamination and size of the hippocampus and cerebellum in Shuffler mice progressively deteriorate compared to in wild-type mice

• Shuffler mice exhibit disorganized neuronal lamination with abnormal dispersal of the CA3 field compared to in wild-type mice

abnormal dentate gyrus morphology ( J:156098 )

• the suprapyramidal blade of the dentate gyrus in the rostral and medial portions of most Shuffler hippocampus is missing unlike in wild-type mice

small hippocampus ( J:156098 )

• in most Shuffler mice at P2 and P60, especially caudally

abnormal cerebellum morphology ( J:156098 )

• at P10, neuronal lamination and size of the hippocampus and cerebellum in Shuffler mice progressively deteriorate compared to in wild-type mice

• at P60, Shuffler mice exhibit a disorganized cerebellum unlike in wild-type mice

• Shuffler mice exhibit abnormal lamination of the cerebellum unlike wild-type mice

• mildly affected Shuffler mice exhibit abnormalities throughout the entire cerebellum while severely affected Shuffler mice exhibit defects in the rostral cerebellar lobes

abnormal cerebellum external granule cell layer morphology ( J:156098 )

• contains ectopic masses composed of neuronal and glial cells in Shuffler mice

thin external granule cell layer ( J:156098 )

• in Shuffler mice at P2, but not P10

abnormal cerebellar cortex morphology ( J:156098 )

• at P2, the cerebellar cortex of Shuffler mice exhibits cell loss and disorganization compared to in wild-type mice

• at P60, the cerebellar cortex is thin in Shuffler mice compared to in wild-type mice

• Shuffler mice exhibit delamination and disorganization of Purkinje cells, granule cells, and Bergmann glia compared with wild-type mice

• Shuffler mice exhibit disrupted Bergmann glia morphology and lamination compared with wild-type mice

• however, cortical lamination is normal at P10

abnormal cerebellar lobule formation ( J:156098 )

• severely affected Shuffler mice exhibit fused lobes unlike in wild-type mice

abnormal cerebellar Purkinje cell layer ( J:156098 )

• Purkinje cells in Shuffler mice are dispersed and less organized than in wild-type mice

delaminated Purkinje cell layer ( J:156098 )

• in Shuffler mice

abnormal cerebellar granule layer morphology ( J:156098 )

• disorganized in Shuffler mice

ectopic cerebellar granule cells ( J:156098 )

• in some Shuffler mice

delaminated cerebellar granule layer ( J:156098 )

• in Shuffler mice

small cerebellum ( J:156098 )

• in Shuffler mice at P2 and P10

abnormal postnatal subventricular zone morphology ( J:156098 )

• at P2, the subventricular zone of Shuffler mice accumulates cells unlike in wild-type mice

• however, the subventricular zone is normal at P10

behavior/neurological

abnormal behavior ( J:156098 )

• Background Sensitivity: mice further backcrossed to 129S/SvEv exhibit behavioral and neurological defects identified as the Shuffler phenotype unlike mice further backcrossed to C57BL/6J mice

poor grooming ( J:156098 )

• at weaning but not at later time points

abnormal motor capabilities/coordination/movement ( J:156098 )

• Shuffler mice develop motor defects and die apparently due to malnutrition

ataxia ( J:156098 )

• in Shuffler mice

abnormal gait ( J:156098 )

• in Shuffler mice

growth/size/body

decreased body size ( J:156098 )

• at weaning but not at later time points

cellular

abnormal radial glial cell morphology ( J:156098 )

• at P2, radial glial cells in Shuffler mice that stretch across the cortical layers are not as prominent or organized as in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
oculodentodigital dysplasia		DOID:0060291	OMIM:164200 OMIM:257850	J:156098