PUBLICATION
The Zebrafish Progranulin Gene Family and Antisense Transcripts
- Authors
- Cadieux, B., Chitramuthu, B.P., Baranowski, D., and Bennett, H.P.
- ID
- ZDB-PUB-051114-8
- Date
- 2005
- Source
- BMC Genomics 6(1): 156 (Journal)
- Registered Authors
- Cadieux, Benoit
- Keywords
- none
- MeSH Terms
-
- Amino Acid Motifs
- Amino Acid Sequence
- Animals
- Blotting, Northern
- Chromatography, High Pressure Liquid
- Chromosome Mapping
- Cloning, Molecular
- DNA, Complementary/metabolism
- Gene Dosage
- Gene Expression Regulation, Developmental*
- Gene Library
- Humans
- In Situ Hybridization
- Intercellular Signaling Peptides and Proteins/biosynthesis
- Intercellular Signaling Peptides and Proteins/genetics*
- Models, Genetic
- Molecular Sequence Data
- Multigene Family
- Oligonucleotides, Antisense/chemistry
- Oligonucleotides, Antisense/genetics*
- Phylogeny
- RNA/metabolism
- RNA, Messenger/metabolism
- Reverse Transcriptase Polymerase Chain Reaction
- Sequence Homology, Amino Acid
- Tissue Distribution
- Transcription, Genetic
- Zebrafish
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 16277664 Full text @ BMC Genomics
Citation
Cadieux, B., Chitramuthu, B.P., Baranowski, D., and Bennett, H.P. (2005) The Zebrafish Progranulin Gene Family and Antisense Transcripts. BMC Genomics. 6(1):156.
Abstract
BACKGROUND: Progranulin is an epithelial tissue growth factor (also known as proepithelin, acrogranin and PC-cell-derived growth factor) that has been implicated in development, wound healing and in the progression of many cancers. The single mammalian progranulin gene encodes a glycoprotein precursor consisting of seven and one half tandemly repeated non-identical copies of the cystine-rich granulin motif. A genome-wide duplication event hypothesized to have occurred at the base of the teleost radiation predicts that mammalian progranulin may be represented by two co-orthologues in zebrafish. RESULTS: The cDNAs encoding two zebrafish granulin precursors, progranulins-A and -B, were characterized and found to contain 10 and 9 copies of the granulin motif respectively. The cDNAs and genes encoding two additional forms of granulin, progranulins -1 and -2, were also cloned and sequenced. Both latter peptides were found to be encoded by precursors with a simplified architecture consisting of one and one half copies of the granulin motif. A cDNA encoding a chimeric progranulin which likely arises through the mechanism of trans-splicing between grn1 and grn2 was also characterized. A non-coding RNA gene with antisense complementarity to both grn1 and grn2 was identified which may have functional implications with respect to gene dosage, as well as in restricting the formation of the chimeric form of progranulin. Chromosomal localization of the four progranulin (grn) genes reveals syntenic conservation for grna only, suggesting that it is the true orthologue of mammalian grn. RT-PCR and whole-mount in situ hybridization analysis of zebrafish grns during development reveals that combined expression of grna and grnb, but not grn1 and grn2, recapitulate many of the expression patterns observed for the murine counterpart. This includes maternal deposition, widespread central nervous system distribution and specific localization within the epithelial compartments of various organs. CONCLUSION: In support of the duplication-degeneration-complementation model of duplicate gene retention, partitioning of expression between grna and grnb was observed in the intermediate cell mass and yolk syncytial layer, respectively. Taken together these expression patterns suggest that the function of an ancestral grn gene has been devolved upon four paralogues in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping