Role of AlkB homologs 1 and 7 (ABH1 and 7) in epigenetic reprogramming

This project is primarily based upon the intriguing phenotype and breeding pattern of mABH1 (mouse AlkB homolog 1) targeted mice. As outlined below, this dioxygenase is required for faithful embryonic development. Major developmental defects include failu re of eye, nose and limb development (Figure 1). Furthermore, the ratio between female and male birth is considerably skewed against female births (Figure 2). We suggest that ABH1, and possible ABH7 is required for epigenetic reprogramming and propose tha t our initial phenotyping results of mABH1 targeted mice partly can be explained by; (I) mABH1 expression peak at day 11 during mouse embryogenesis (dpc). This match well with the expression of PAX6 and other genes required for eye development. Transcript ion profiling of 11 dpc wild-type and mABH1 targeted embryos will be carried out to elucidate regulatory mechanisms associated with mABH1 deficiency. (II) hABH1 interact with a testis specific ZBTB transcription factor (zinc finger and BTB domain contain ing; Figure 3). Thus, it is possible that ABH1 is involved in epigenetic reprogramming, including meiotic sex chromosome inactivation during spermatogenesis. Based on 2-hybrid screens and bioinformatics analysis, there are some remarkable similarities be tween ABH1 and ABH7 (also named Spata11; spermatogenesis associated 11), which is described in more detail below.