Mice Lacking Alkbh1 Display Sex-Ratio Distortion and Unilateral Eye DefectsReportar como inadecuado




Mice Lacking Alkbh1 Display Sex-Ratio Distortion and Unilateral Eye Defects - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Line M. Nordstrand, Jessica Svärd , Elisabeth Larsen , Anja Nilsen , Rune Ougland , Kari Furu , Guro F. Lien, Torbjørn Rognes,

Fuente: http://plos.srce.hr/



DESCARGAR PDF




Documentos relacionados