PUBLICATION
Graded phenotypic response to partial and complete deficiency of a brain-specific transcript variant of the winged helix transcription factor RFX4
- Authors
- Blackshear, P.J., Graves, J.P., Stumpo, D.J., Cobos, I., Rubenstein, J.L., and Zeldin, D.C.
- ID
- ZDB-PUB-040813-7
- Date
- 2003
- Source
- Development (Cambridge, England) 130(19): 4539-4552 (Journal)
- Registered Authors
- Keywords
- Hydrocephalus, Regulatory factor X, Winged helix transcription factor, Cortex, Midline, Mouse
- MeSH Terms
-
- Alternative Splicing*
- Amino Acid Sequence
- Animals
- Brain/anatomy & histology
- Brain/embryology*
- Brain/pathology
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism*
- Embryo, Mammalian/anatomy & histology
- Embryo, Mammalian/pathology*
- Embryo, Mammalian/physiology
- Helix-Turn-Helix Motifs
- Humans
- Hydrocephalus/genetics
- Hydrocephalus/pathology
- In Situ Hybridization
- Mice
- Mice, Transgenic
- Molecular Sequence Data
- Phenotype
- Protein Isoforms/genetics
- Protein Isoforms/metabolism*
- Sequence Alignment
- Tissue Distribution
- Transcription Factors/chemistry
- Transcription Factors/genetics
- Transcription Factors/metabolism*
- PubMed
- 12925582 Full text @ Development
Citation
Blackshear, P.J., Graves, J.P., Stumpo, D.J., Cobos, I., Rubenstein, J.L., and Zeldin, D.C. (2003) Graded phenotypic response to partial and complete deficiency of a brain-specific transcript variant of the winged helix transcription factor RFX4. Development (Cambridge, England). 130(19):4539-4552.
Abstract
One line of mice harboring a cardiac-specific epoxygenase transgene developed head swelling and rapid neurological decline in young adulthood, and had marked hydrocephalus of the lateral and third ventricles. The transgene was found to be inserted into an intron in the mouse Rfx4 locus. This insertion apparently prevented expression of a novel variant transcript of RFX4 (RFX4_v3), a member of the regulatory factor X family of winged helix transcription factors. Interruption of two alleles resulted in profound failure of dorsal midline brain structure formation and perinatal death, presumably by interfering with expression of downstream genes. Interruption of a single allele prevented formation of the subcommissural organ, a structure important for cerebrospinal fluid flow through the aqueduct of Sylvius, and resulted in congenital hydrocephalus. These data implicate the RFX4_v3 variant transcript as being crucial for early brain development, as well as for the genesis of the subcommissural organ. These findings may be relevant to human congenital hydrocephalus, a birth defect that affects 0.6 per 1000 newborns.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping