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The mouse formin (Fmn) gene: abundant circular RNA transcripts and gene-targeted deletion analysis
1Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Molecular Medicine (Cambridge, Mass.)
|December 16, 1998
Summary
Novel circular RNAs from the formin (Fmn) gene were discovered. Mice lacking these circular Fmn RNAs exhibit kidney development defects, suggesting their crucial role in renal agenesis.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Mutations in the mouse formin (Fmn) gene are linked to limb deformities and renal aplasia.
- A molecular genetic approach was employed to investigate novel circular RNAs from the Fmn gene.
Purpose of the Study:
- To characterize novel circular RNA transcripts from the Fmn gene.
- To understand the developmental implications of gene-targeted mutations affecting Fmn.
Main Methods:
- RT-PCR and ribonuclease protection analyses were used to identify and characterize circular RNA transcripts.
- Gene-targeted homologous recombination was utilized to create mouse lines with deletions of specific Fmn exons (exon 4 or exon 5).
Main Results:
- Novel circular RNA transcripts with reversed exon order were identified as major transcripts in adult brain and kidney.
- Mice lacking these circular Fmn RNAs showed normal limb development but exhibited variable renal aplasia.
- Linear RNA isoforms of Fmn were produced normally in the mutant mice.
Conclusions:
- The study identified novel circular Fmn RNAs, suggesting they play a biological role beyond aberrant splicing.
- The absence of circular Fmn RNAs in mutant mice correlates with an incompletely penetrant renal agenesis phenotype.
- These findings implicate circular Fmn RNAs in kidney development.