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Comment |
Transcriptome analysis reveals an unexpected role of a collagen tyrosine kinase receptor gene, Ddr2, as a regulator of ovarian function. Matsumura H et al. Mice homozygous for the smallie (slie) mutation lack a collagen receptor, discoidin domain receptor 2 (DDR2), and are dwarfed and infertile due to peripheral dysregulation of the endocrine system of unknown etiology. We used a systems biology approach to identify biological networks affected by Ddr2(slie/slie) mutation in ovaries using microarray analysis and validate findings using molecular, cellular and functional biological assays. Transcriptome analysis indicated several altered gene categories in Ddr2(slie/slie) mutants, including gonadal development; ovulation; anti-apoptosis; and steroid hormones. Subsequent biological experiments confirmed the transcriptome analysis predictions. For instance, a significant increase of TUNEL-positive follicles was found in Ddr2(slie/slie) mutants vs. wildtype, which confirm the transcriptome prediction for decreased chromatin maintenance and anti-apoptosis. Decreases in gene expression were confirmed by RT-PCR and/or qPCR luteinizing hormone receptor and prostaglandin type E & F receptors in Ddr2(slie/slie) mutants, compared to wildtype, confirm hormonal signaling pathways involved in ovulation. Furthermore, deficiencies in immunohistochemistry for DDR2 and luteinizing hormone receptor in the somatic cells, but not the oocytes, of Ddr2(slie/slie) mutant ovaries and suggest against an intrinsic defect in germ cells. Indeed, Ddr2(slie/slie) mutants ovulated significantly fewer oocytes; their oocytes were competent to complete meiosis and fertilization in vitro. Taken together, our convergent data signify DDR2 as a novel critical player in ovarian function, which acts upon classical endocrine pathways in somatic, rather than germline, cells. Key words: discoidin domain receptor, prostaglandin receptor, ovulation, luteinizing hormone receptor.
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Mutations |
1 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: Transcriptome analysis reveals an unexpected role of a collagen tyrosine kinase receptor gene, Ddr2, as a regulator of ovarian function. Matsumura H et al. Mice homozygous for the smallie (slie) mutation lack a collagen receptor, discoidin domain receptor 2 (DDR2), and are dwarfed and infertile due to peripheral dysregulation of the endocrine system of unknown etiology. We used a systems biology approach to identify biological networks affected by Ddr2(slie/slie) mutation in ovaries using microarray analysis and validate findings using molecular, cellular and functional biological assays. Transcriptome analysis indicated several altered gene categories in Ddr2(slie/slie) mutants, including gonadal development; ovulation; anti-apoptosis; and steroid hormones. Subsequent biological experiments confirmed the transcriptome analysis predictions. For instance, a significant increase of TUNEL-positive follicles was found in Ddr2(slie/slie) mutants vs. wildtype, which confirm the transcriptome prediction for decreased chromatin maintenance and anti-apoptosis. Decreases in gene expression were confirmed by RT-PCR and/or qPCR luteinizing hormone receptor and prostaglandin type E & F receptors in Ddr2(slie/slie) mutants, compared to wildtype, confirm hormonal signaling pathways involved in ovulation. Furthermore, deficiencies in immunohistochemistry for DDR2 and luteinizing hormone receptor in the somatic cells, but not the oocytes, of Ddr2(slie/slie) mutant ovaries and suggest against an intrinsic defect in germ cells. Indeed, Ddr2(slie/slie) mutants ovulated significantly fewer oocytes; their oocytes were competent to complete meiosis and fertilization in vitro. Taken together, our convergent data signify DDR2 as a novel critical player in ovarian function, which acts upon classical endocrine pathways in somatic, rather than germline, cells. Key words: discoidin domain receptor, prostaglandin receptor, ovulation, luteinizing hormone receptor.
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