RGD Reference Report - Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome. - Rat Genome Database

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Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome.

Authors: Parente, Martina  Tonini, Claudia  Buzzelli, Valeria  Carbone, Emilia  Trezza, Viviana  Pallottini, Valentina 
Citation: Parente M, etal., Int J Mol Sci. 2022 Mar 21;23(6):3408. doi: 10.3390/ijms23063408.
RGD ID: 405100966
Pubmed: PMID:35328827   (View Abstract at PubMed)
PMCID: PMC8955806   (View Article at PubMed Central)
DOI: DOI:10.3390/ijms23063408   (Journal Full-text)

Fragile X Syndrome (FXS) is the most frequent form of inherited X-linked pathology, associated with an intellectual and developmental disability, and currently considered the first monogenic cause of autism spectrum disorder (ASD). Low levels of total cholesterol reported in the serum of FXS patients, and evidence that FMRP targets a subset of mRNAs encoding proteins of lipid synthesis and transport suggests that the cholesterol metabolism impairments could be involved in FXS. Thus, the aim of the presented work was to investigate the modulations of the cholesterol biosynthetic pathway and its end-products in a recently developed Fmr1-Δexon 8 rat model of FXS. Here, we show that this experimental model mimics what is found in FXS patients, exhibiting a lower serum cholesterol content, accompanied by a reduction in food intake and body weight compared to WT animals. Moreover, alterations of proteins committed to cholesterol synthesis and uptake have been observed in the amygdala, prefrontal cortex and nucleus accumbens. Interestingly, the end-products show a brain region-dependent modulation in Fmr1-Δexon 8 rats. Overall, our results demonstrate that the cholesterol biosynthetic pathway is altered in some brain regions of this preclinical model of FXS. This finding has relevance for future studies to delve deeper into the involvement of this metabolic process in FXS, and thus its possible role as a therapeutic target.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fmr1Ratdecreased body weight  IMP compared to wild typeRGD 
Fmr1em1SageRatdecreased body weight  IMP compared to wild typeRGD 
SD-Fmr1em1SageRatdecreased body weight  IMP compared to wild typeRGD 
Fmr1Ratdecreased circulating cholesterol level  IMP compared to wild typeRGD 
Fmr1em1SageRatdecreased circulating cholesterol level  IMP compared to wild typeRGD 
SD-Fmr1em1SageRatdecreased circulating cholesterol level  IMP compared to wild typeRGD 
Fmr1Ratdecreased food intake  IMP compared to wild typeRGD 
Fmr1em1SageRatdecreased food intake  IMP compared to wild typeRGD 
SD-Fmr1em1SageRatdecreased food intake  IMP compared to wild typeRGD 
Fmr1Ratdecreased liver cholesterol level  IMP compared to wild typeRGD 
Fmr1em1SageRatdecreased liver cholesterol level  IMP compared to wild typeRGD 
SD-Fmr1em1SageRatdecreased liver cholesterol level  IMP compared to wild typeRGD 
Objects Annotated

Genes (Rattus norvegicus)
Fmr1  (fragile X messenger ribonucleoprotein 1)
Fmr1em1Sage  (FMRP translational regulator 1; zinc finger nuclease induced mutant 1, Sigma Advanced Genetic Engineering Labs)

Strains
SD-Fmr1em1Sage  (NA)


Additional Information