OtherMolecular autism2017

RNA sequencing and proteomics approaches reveal novel deficits in the cortex of Mecp2-deficient mice, a model for Rett syndrome.

Natasha L Pacheco, Michael R Heaven, Leanne M Holt and 5 others

PMID 29090078

WHAT IT FOUND

Symptomatic mice modeling Rett syndrome showed many altered genes and proteins in cortex, including metabolism and stress-response pathways.

These are molecular observations, not tested treatments, and they do not change patient care.

Key findings

01RNA sequencing of symptomatic Mecp2-deficient mouse cortex identified 391 significantly altered genes, with 132 increased and 259 decreased.

02Proteomics of the same cortical tissue identified 465 significant protein changes among 4789 quantified proteins, with 299 increased and 166 decreased.

03Gene and protein changes were not well matched overall, but 35 genes and their corresponding proteins were both significant.

STILL TO COME

How it was doneWhat they found

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What it does not show

The study was done in mice, not humans, so it does not show what works in patients. Only symptomatic male mice were studied; the paper notes that heterozygous female mice are more clinically relevant for Rett syndrome. The researchers used whole cortex homogenate, so changes in one cell type could be diluted or masked by other cell types. Protein significance was judged at p < 0.1, a less strict cutoff than p < 0.05. The paper reports molecular changes, not clinical outcomes or treatment effects.

Declared interests

Funded by the National Institute of Neurological Disorders and Stroke, the Civitan Emerging Research Scholar Award at the University of Alabama at Birmingham, and the Comprehensive Cancer Center at the University of Alabama at Birmingham. The supplied text does not include an author competing-interests statement.

The easy way to misread this

Do not treat these gene and protein changes as a Rett syndrome treatment. They were measured in symptomatic male mouse cortex, not in patients, and no therapy or clinical outcome was tested.

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The study

Participants
4 biological replicates per genotype
Certainty of evidence
Low

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    Cite

    Natasha L Pacheco, Michael R Heaven, Leanne M Holt, et al. RNA sequencing and proteomics approaches reveal novel deficits in the cortex of Mecp2-deficient mice, a model for Rett syndrome. Molecular autism. 2017.

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