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DDC-4, an apoptosis-associated gene, is a secreted frizzled relative
V Wolf1, G Ke, A M Dharmarajan
1Department of Clinical Research, University of Berne, Switzerland.
Abstract:
The differential display method has been used in our laboratory as a coincidence analysis to isolate genes expressed in common in each of three different rat tissues undergoing physiological apoptosis: mammary gland, ovarian corpus luteum and ventral prostate. The most interesting of these isolates, DDC-4, shows a clear association with apoptosis, its expression being confined to these three organs, and only during their involution. Using DDC-4 as probe, we screened a rat ovarian cDNA library to obtain full-length isolates. One isolate, Y81 clone 40, gives rise to a protein of approximately 40 kDa with coupled in vitro transcription/translation. Sequencing of this clone indicates an open reading frame of 1044 nucleotides encoding a protein of 39.7 kDa with a putative signal sequence. This clone exhibits a high homology with the cysteine-rich domain, i.e. the ligand-binding domain, of the fizzled gene family originally defined as tissue polarity genes in Drosophila. The homology of Y81 clone 40 is most extensive with the newly described secreted frizzled relatives, the frzb subfamily.
Insights
Researchers identified a novel gene, DDC-4, associated with apoptosis in rat tissues. This gene, homologous to secreted frizzled related proteins, may play a role in physiological tissue involution.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Physiological apoptosis occurs in specific rat tissues, including mammary gland, ovarian corpus luteum, and ventral prostate.
- Identifying genes involved in tissue-specific apoptosis is crucial for understanding developmental and degenerative processes.
Purpose of the Study:
- To isolate and characterize genes commonly expressed during physiological apoptosis in rat mammary gland, ovarian corpus luteum, and ventral prostate.
- To identify novel genes involved in the involution of these specific tissues.
Main Methods:
- Differential display method was employed for coincidence analysis to identify commonly expressed genes.
- A rat ovarian cDNA library was screened using the DDC-4 gene as a probe.
- In vitro transcription/translation and DNA sequencing were performed on isolated clones.
Main Results:
- A gene isolate, DDC-4, was identified, showing specific expression in the three studied tissues during involution.
- A full-length clone, Y81 clone 40, was obtained, encoding a protein of approximately 39.7 kDa with a putative signal sequence.
- Y81 clone 40 demonstrated significant homology to the ligand-binding domain of the frizzled gene family, particularly the secreted frizzled related protein (sfrp) subfamily.
Conclusions:
- The DDC-4 gene is specifically associated with physiological apoptosis and involution in the mammary gland, ovarian corpus luteum, and ventral prostate of rats.
- The identified clone Y81 clone 40 represents a novel secreted frizzled related protein, potentially involved in apoptosis regulation.
- This finding provides new insights into the molecular mechanisms underlying tissue-specific apoptosis and involution.