RGD Reference Report - Phenotypic characterization of nonsocial behavioral impairment in neurexin 1a knockout rats. - Rat Genome Database

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Phenotypic characterization of nonsocial behavioral impairment in neurexin 1a knockout rats.

Authors: Esclassan, Frederic  Francois, Jennifer  Phillips, Keith G  Loomis, Sally  Gilmour, Gary 
Citation: Esclassan F, etal., Behav Neurosci. 2015 Feb;129(1):74-85. doi: 10.1037/bne0000024. Epub 2014 Nov 24.
RGD ID: 12914797
Pubmed: PMID:25420124   (View Abstract at PubMed)
DOI: DOI:10.1037/bne0000024   (Journal Full-text)

Neurexins are neuronal presynaptic proteins that play a key role in mediation of synapse formation. Heterozygous partial deletions in the neurexin-1 gene (NRXN1, 2p16.3) have been observed in autism spectrum disorder (ASD) patients. NRXN1-α knockout (KO) mice present behavioral impairments that resemble some of the core ASD symptoms of social impairment and inflexibility/stereotypy. At present, a thorough assessment of cognitive function has yet to be completed. Rats, containing a biallelic deletion of the NRNX1-α gene on a Sprague Dawley background were compared to littermate wild types across a range of tasks designed to test functional domains disrupted in ASD and other neurodevelopmental disorders, including sensory perception (prepulse inhibition), attention (latent inhibition), associative learning (instrumental and Pavlovian conditioning), and memory (rewarded alternation T maze and spatial discrimination). NRXN1α KO rats were found to present with large and persistent nonsocial deficits, including hyperactivity, deficits in simple instrumental learning, latent inhibition, and spatial-dependent learning. No deficit in sensorimotor gating was observed, despite the presence of an exaggerated startle response. Although KO animals were also able to learn a simple Pavlovian conditioning discrimination, they did display impaired latent inhibition. The presence of pronounced impairments in several domains in NRXN1α KO rats clearly suggests that nonsocial cognitive deficits can also be measured in an animal model of ASD. Further exploration of those deficits, both clinically and preclinically, as planned in the Innovative Medicines Initiative's European Autism Interventions: A Multicenter Study for Developing New Medications program, may help to better understand the brain circuitry involved in ASD and therefore open new avenues to advance novel therapies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
autism spectrum disorder  ISONrxn1 (Rattus norvegicus)12914797; 12914797 RGD 
autism spectrum disorder  IMP 12914797; 12914797; 12914797 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal habituation to a new environment  IMP 12914797; 12914797; 12914797 RGD 
decreased body weight  IMP 12914797; 12914797; 12914797compared to wild type littermateRGD 
hyperactivity  IMP 12914797; 12914797; 12914797 RGD 
impaired discrimination learning sexual_dimorphism IMP 12914797; 12914797; 12914797compared to wild type maleRGD 
increased startle reflex  IMP 12914797; 12914797; 12914797compared to wild type littermateRGD 
Objects Annotated

Genes (Rattus norvegicus)
Nrxn1  (neurexin 1)
Nrxn1em1  (neurexin 1; zinc finger nuclease induced mutant 1, Sigma Advanced Genetic Engineering Labs)

Genes (Mus musculus)
Nrxn1  (neurexin I)

Genes (Homo sapiens)
NRXN1  (neurexin 1)

Strains
SD-Nrxn1em1Sage  (NA)


Additional Information