RGD Reference Report - Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function. - Rat Genome Database

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Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function.

Authors: Ntoulas, George  Brakatselos, Charalampos  Nakas, Gerasimos  Asprogerakas, Michail-Zois  Delis, Foteini  Leontiadis, Leonidas J  Trompoukis, George  Papatheodoropoulos, Costas  Gkikas, Dimitrios  Valakos, Dimitrios  Vatsellas, Giannis  Politis, Panagiotis K  Polissidis, Alexia  Antoniou, Katerina 
Citation: Ntoulas G, etal., Transl Psychiatry. 2024 Feb 20;14(1):104. doi: 10.1038/s41398-024-02815-0.
RGD ID: 401976422
Pubmed: PMID:38378836   (View Abstract at PubMed)
DOI: DOI:10.1038/s41398-024-02815-0   (Journal Full-text)

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and the most prevalent monogenic cause of autism. Although the knockout (KO) of the Fmr1 gene homolog in mice is primarily used for elucidating the neurobiological substrate of FXS, there is limited association of the experimental data with the pathophysiological condition in humans. The use of Fmr1 KO rats offers additional translational validity in this regard. Therefore, we employed a multi-level approach to study the behavioral profile and the glutamatergic and GABAergic neurotransmission status in pathophysiology-associated brain structures of Fmr1 KO rats, including the recordings of evoked and spontaneous field potentials from hippocampal slices, paralleled with next-generation RNA sequencing (RNA-seq). We found that these rats exhibit hyperactivity and cognitive deficits, along with characteristic bidirectional glutamatergic and GABAergic alterations in the prefrontal cortex and the hippocampus. These results are coupled to affected excitability and local inhibitory processes in the hippocampus, along with a specific transcriptional profile, highlighting dysregulated hippocampal network activity in KO rats. Overall, our data provide novel insights concerning the biobehavioral profile of FmR1 KO rats and translationally upscales our understanding on pathophysiology and symptomatology of FXS syndrome.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fmr1Ratintracellular glutamate homeostasis  IMP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fmr1Rathyperactivity  IMP  RGD 
Fmr1em2McwiRathyperactivity  IMP  RGD 
LE-Fmr1em2McwiRathyperactivity  IMP compared to wild type controlsRGD 
Fmr1Ratimpaired short-term object recognition memory  IMP compared to wild type controlsRGD 
Fmr1em2McwiRatimpaired short-term object recognition memory  IMP compared to wild type controlsRGD 
LE-Fmr1em2McwiRatimpaired short-term object recognition memory  IMP compared to wild type controlsRGD 
Fmr1Ratimpaired spatial learning  IMP  RGD 
Fmr1em2McwiRatimpaired spatial learning  IMP  RGD 
LE-Fmr1em2McwiRatimpaired spatial learning  IMP compared to wild type controlsRGD 
Fmr1Ratincreased paired-pulse inhibition  IMP  RGD 
Fmr1em2McwiRatincreased paired-pulse inhibition  IMP  RGD 
LE-Fmr1em2McwiRatincreased paired-pulse inhibition  IMP compared to wild type controlsRGD 
Objects Annotated

Genes (Rattus norvegicus)
Fmr1  (fragile X messenger ribonucleoprotein 1)
Fmr1em2Mcwi  (FMRP translational regulator 1; CRISPR/Cas9 induced mutant 2, Medical College of Wisconsin)

Strains
LE-Fmr1em2Mcwi  (NA)


Additional Information