Gene dosage of Otx2 is important for fertility in male mice
| Autor: | Susan L. Mayo, Pamela L. Mellon, Daniel D. Clark, Jason D. Meadows, Ikuo Kimura, Rachel Larder |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty endocrine system Aging Heterozygote Transcription Genetic Gene Dosage Hypothalamic–pituitary–gonadal axis Gonadotropin-releasing hormone Gonadotrophs Biology Biochemistry Gene dosage Article Gonadotropin-Releasing Hormone Mice Endocrinology Cell Movement Internal medicine medicine Animals RNA Messenger Molecular Biology Transcription factor Alleles Otx Transcription Factors Luteinizing Hormone Axons Fertility Gene Expression Regulation Hypothalamus Eye development Homeobox hormones hormone substitutes and hormone antagonists Gonadotropins Hormone |
| Popis: | Together, the hypothalamus, pituitary and gonads direct the development and regulation of reproductive function in mammals. Gonadotropin-releasing hormone (GnRH) expression is limited to ∼800 neurons that originate in the olfactory placode then migrate to the hypothalamus. Coordination of the hypothalamic–pituitary–gonadal (HPG) axis is dependent upon correct neuronal migration of GnRH neurons into the hypothalamus followed by proper synthesis and pulsatile secretion of GnRH. Defects in any one of these processes causes infertility. Otx2, the vertebrate homologue of Drosophila orthodenticle, is a transcription factor that has been shown to be critical for normal brain and eye development and is expressed in both the developing GnRH neurons and the pituitary, suggesting that this gene may play a critical role in development of the HPG axis. As Otx2-null mice are embryonic lethal, we have analyzed the reproductive capacity of heterozygous Otx2 mice to determine the contribution of Otx2 gene dosage to normal HPG axis function. Our data reveal that correct dosage of Otx2 is critical for normal fertility as loss of one allele of Otx2 leads to a discernible reproductive phenotype in male mice due to disruption of the migration of GnRH neurons during development. |
| Databáze: | OpenAIRE |
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