PAFAH1B1(+/-) adolescent mice showed significant reductions in elimination and turnover rates of dendritic protrusions of layer V pyramidal neurons and exhibited deficits in social interaction (Sudarov et al., 2013).
Molecular Function
Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. Mutations in this gene are responsible for lissencephaly 1 (LIS1) [MIM:607432].
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Lis1 controls dynamics of neuronal filopodia and spines to impact synaptogenesis and social behaviour.
Abnormalities in Cortical GABAergic Interneurons of the Primary Motor Cortex Caused by Lis1 (Pafah1b1) Mutation Produce a Non-drastic Functional Phenotype
PAFAH1B1 playes prominently in dendritic filopodia dynamics and spine turnover implicating reduced dendritic spine density as contributing to developmental autistic-like behavior.
References
Type
Title
Author, Year
Primary
Lis1 controls dynamics of neuronal filopodia and spines to impact synaptogenesis and social behaviour.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Targeted replacement of part of exon 6 and all of exon 7 with PGKneo in the opposite transcriptional orientation relative to Pafah1b1 (Fig. 1a). The neo disruption eliminates amino acids 164-214 and introduces multiple stop codons into exon 6.
Allele Type: Strain of Origin: Not specified
Genetic Background: Not Specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 3-6 of the PAFAH1B1 gene using CamkII-cre in excitatory neurons of the forebrain
Allele Type: Conditional loss-of-function
Strain of Origin: Not specified
Genetic Background: Not Specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Description: Decreased turnover and elimination rates of filopodia in layer v pyramidal neurons
Exp Paradigm: Transcranial two photon microscopy of layer v pyramidal neurons
Description: Decreased social novelty recognition indicated by no preference for close interactions with either stranger 1 or stranger 2 mouse
Exp Paradigm: Social novelty recognition testing
Description: Decreased social behavior indicated by more time spent in compartment and in close proximity with empty cup
Exp Paradigm: Three-chamber social arena
Description: Decreaesd social novelty recognition indicated by similar amounts of time in both compartments and interaction zones
Exp Paradigm: Three-chamber social arena
