RGD Reference Report - Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep-Wake Physiology. - Rat Genome Database

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Cntnap2 Knockout Rats and Mice Exhibit Epileptiform Activity and Abnormal Sleep-Wake Physiology.

Authors: Thomas, Alexia M  Schwartz, Michael D  Saxe, Michael D  Kilduff, Thomas S 
Citation: Thomas AM, etal., Sleep. 2017 Jan 1;40(1). doi: 10.1093/sleep/zsw026.
RGD ID: 12880397
Pubmed: PMID:28364455   (View Abstract at PubMed)
DOI: DOI:10.1093/sleep/zsw026   (Journal Full-text)


Study Objectives: Although recent innovations have enabled modification of the rat genome, it is unclear whether enhanced utility of rodents as human disease models will result. We compared electroencephalogram (EEG) and behavioral phenotypes of rats and mice with homozygous deletion of Cntnap2, a gene associated with cortical dysplasia-focal epilepsy (CDFE) and autism spectrum disorders (ASD).
Methods: Male contactin-associated protein-like 2 (Cntnap2) knockout (KO) and wild-type (WT) rats and male Cntnap2 KO and WT mice were implanted with telemeters to record EEG, electromyogram, body temperature, and locomotor activity. Animals were subjected to a test battery for ASD-related behaviors, followed by 24-hr EEG recordings that were analyzed for sleep-wake parameters and subjected to spectral analysis.
Results: Cntnap2 KO rats exhibited severe motor seizures, hyperactivity, and increased consolidation of wakefulness and REM sleep. By contrast, Cntnap2 KO mice demonstrated absence seizure-like events, hypoactivity, and wake fragmentation. Although seizures observed in Cntnap2 KO rats were more similar to those in CDFE patients than in KO mice, neither model fully recapitulated the full spectrum of disease symptoms. However, KOs in both species had reduced spectral power in the alpha (9-12 Hz) range during wake, suggesting a conserved EEG biomarker.
Conclusions: Deletion of Cntnap2 impacts similar behaviors and EEG measures in rats and mice, but with profound differences in nature and phenotypic severity. These observations highlight the importance of cross-species comparisons to understand conserved gene functions and the limitations of single- species models to provide translational insights relevant to human diseases.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CNTNAP2Humanepilepsy  ISOCntnap2 (Rattus norvegicus) RGD 
CNTNAP2Humanepilepsy  ISOCntnap2 (Rattus norvegicus) and Cntnap2 (Mus musculus) RGD 
Cntnap2Ratepilepsy  IMP  RGD 
Cntnap2Mouseepilepsy  ISOCntnap2 (Rattus norvegicus) RGD 
Cntnap2Mouseepilepsy  IMP  RGD 
Cntnap2em1SageRatepilepsy  IMP  RGD 
SD-Cntnap2em1SageRatepilepsy  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Objects Annotated

Genes (Rattus norvegicus)
Cntnap2  (contactin associated protein 2)
Cntnap2em1Sage  (contactin associated protein-like 2; zinc finger nuclease induced mutant 1, Sigma Advanced Genetic Engineering Labs)

Genes (Mus musculus)
Cntnap2  (contactin associated protein-like 2)

Genes (Homo sapiens)
CNTNAP2  (contactin associated protein 2)

Strains
SD-Cntnap2em1Sage  (NA)


Additional Information