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Related Experiment Video

Updated: May 13, 2026

Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay

Quantitative Analysis of Alternative Pre-mRNA Splicing in Mouse Brain Sections Using RNA In Situ Hybridization Assay

Published on: August 26, 2018

FMR1 transcript isoforms: association with polyribosomes; regional and developmental expression in mouse brain.

David M Brackett¹, Feng Qing, Paul S Amieux

¹Department of Biochemistry, University of Washington, Seattle, Washington, United States of America.

|March 19, 2013

Summary

The Fragile X Mental Retardation-1 gene (Fmr1) produces multiple protein isoforms, all translated in the brain. Their expression varies by region and developmental stage, impacting Fragile X Syndrome.

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Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing

Isolation of Region-specific Microglia from One Adult Mouse Brain Hemisphere for Deep Single-cell RNA Sequencing

Published on: December 3, 2019

Area of Science:

Neuroscience
Molecular Biology
Genetics

Background:

The Fragile X Mental Retardation-1 gene (Fmr1) is alternatively spliced, producing multiple mRNA and protein isoforms.
These isoforms can have distinct biochemical properties and are found in the central nervous system.

Purpose of the Study:

To investigate the expression levels and distribution of Fmr1 transcript isoforms in the mouse brain.
To understand how isoform expression varies across different brain regions and developmental stages.
To highlight the implications of isoform diversity for Fragile X Syndrome.

Main Methods:

Utilized the RiboTag methodology for precise measurement of transcript isoforms.
Analyzed isoform profiles in whole brain, specific neuronal populations, and across 11 distinct adult brain regions.
Compared adult brain isoform patterns with those in embryonic brain and cultured neural progenitor cells.

Main Results:

All 12 examined Fmr1 transcript isoforms are associated with polyribosomes, indicating translation into Fragile X Mental Retardation Protein (FMRP) isoforms.
Neuronal expression patterns of the 7 most abundant isoforms mirror whole brain distributions.
Hippocampus and olfactory bulb show unique isoform profiles, particularly concerning transcripts encoding an alternate KH RNA binding domain.

Conclusions:

Fmr1 isoform expression is modulated by developmental stage and brain region.
Regional differences in isoform expression, especially in the hippocampus and olfactory bulb, may relate to neuroblast presence.
Loss of all FMRP isoforms in Fragile X Syndrome has complex ramifications due to isoform diversity.