Mice lacking Alkbh1 display sex-ratio distortion and unilateral eye defects
| Autor: | Jessica Svärd, Jeannie T. Lee, Torbjørn Rognes, Elisabeth Larsen, Anja Nilsen, Satoshi H. Namekawa, Arne Klungland, Guro Flor Lien, Kari Furu, Rune Ougland, Line M. Nordstrand |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Embryo Nonmammalian Developmental Biology/Germ Cells Bone Morphogenetic Protein 7 lcsh:Medicine Bone Morphogenetic Protein 2 AlkB Homolog 1 Histone H2a Dioxygenase Bone Morphogenetic Protein 4 Mice Developmental Biology/Molecular Development Testis DNA-(Apurinic or Apyrimidinic Site) Lyase Developmental Biology/Developmental Molecular Mechanisms Microphthalmos Eye Abnormalities lcsh:Science In Situ Hybridization Genetics and Genomics/Genetics of Disease Oligonucleotide Array Sequence Analysis Developmental Biology/Embryology Regulation of gene expression Genetics Mice Knockout Genetics and Genomics/Medical Genetics Multidisciplinary biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Regulation Developmental Embryo Genetics and Genomics/Gene Function Female Research Article Mice 129 Strain Genetics and Genomics/Animal Genetics Offspring AlkB In situ hybridization Dioxygenases Andrology Meiosis Genetics and Genomics/Epigenetics Animals Sex Ratio Allele Spermatogenesis Gene Expression Profiling lcsh:R Anophthalmos Mice Inbred C57BL Animals Newborn Genetics and Genomics/Disease Models biology.protein Developmental Biology/Cell Differentiation lcsh:Q Transcription Factors |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 11, p e13827 (2010) |
| ISSN: | 1932-6203 |
| Popis: | Background Eschericia coli AlkB is a 2-oxoglutarate- and iron-dependent dioxygenase that reverses alkylated DNA damage by oxidative demethylation. Mouse AlkB homolog 1 (Alkbh1) is one of eight members of the newly discovered family of mammalian dioxygenases. Methods and Findings In the present study we show non-Mendelian inheritance of the Alkbh1 targeted allele in mice. Both Alkbh1−/− and heterozygous Alkbh1+/− offspring are born at a greatly reduced frequency. Additionally, the sex-ratio is considerably skewed against female offspring, with one female born for every three to four males. Most mechanisms that cause segregation distortion, act in the male gametes and affect male fertility. The skewing of the sexes appears to be of paternal origin, and might be set in the pachythene stage of meiosis during spermatogenesis, in which Alkbh1 is upregulated more than 10-fold. In testes, apoptotic spermatids were revealed in 5–10% of the tubules in Alkbh1−/− adults. The deficiency of Alkbh1 also causes misexpression of Bmp2, 4 and 7 at E11.5 during embryonic development. This is consistent with the incompletely penetrant phenotypes observed, particularly recurrent unilateral eye defects and craniofacial malformations. Conclusions Genetic and phenotypic assessment suggests that Alkbh1 mediates gene regulation in spermatogenesis, and that Alkbh1 is essential for normal sex-ratio distribution and embryonic development in mice. © 2010 Nordstrand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Databáze: | OpenAIRE |
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