In eukaryotes, introns must be removed from precursor mRNA by the spliceosome. Moreover, each snRNP consists of one or two small nuclear RNAs and many associated proteins, namely pre-mRNA processing proteins. Mutantions in Prp have been shown to be defective in removal of pre-mRNA introns. We have reported that depletion of human p29 downregulated Chk1 phosphorylation upon UV irradiation and resulted in premature chromatin condensation which initiated apoptosis. The distribution of acetylated a-tubulin was significantly reduced and less neurons/neurites appeared in zfp29 morphants compared with uninjected embryos. To further support these neuronal deformities, a wholemount in situ RNA hybridization against HuC, an early pan-neuronal marker in zebrafish, also displayed a significant loss of neuronal cells in the spinal cord in zfp29 morphants. Additionally, knockdown of zfp29 in the Fli transgenic line, which specifically expresses green fluorescence protein in blood vessels, also disturbed the blood vessel formation. Taken together, these results indicated that the abnormities of zfp29 knockdown affected the whole body development and were not restricted to specific tissues. We have generated mp29 knockout mice from the mp29 genetrap embryonic stem cell. Mice carrying a heterozygous insertion between exon 2 and exon 3 of mp29 gene were viable and their offsprings are able to inherit the mutated allele. However, embryos inherited with homozygous insertion in mp29 gene were not viable and mp29GT/GT embryos showed developmental defects at E6.5, partly due to an aberrant DNA damage 1-Tigloyltrichilinin checkpoint in cell cycle. Mass spectrometry analysis identified several major components for pre-mRNA splicing, suggesting an association of mp29 with pre-mRNA complex. Homozygous inactivation of mp29/Syf2 in mice embryos and knockdown of mp29 in NIH-3T3 cells profoundly decrease the expression of atubulin and Chk1. In contrast, no significant effect was on btubulin and Chk2. This result is contrary to the deletion of SYF2 from the previous study in Saccharomyces cerevisiae, which has no notable difference cell cycle progression or in splicing of U3 transcripts. Instead, a lower expression of a-tubulin was only found in double mutant isyl1D and syf2D cells. This conflicted phenomenon can be explained by the low similarity between mouse mp29 and yeast Syf2. There might be different regulatory mechanisms that prevail in these two species. This contention is also supported by the decreased expression of acetylated a-tubulin in zfp29 depleted zebrafish. However, knockdown of human p29 in HeLa and U2OS does not result in an alleviated atubulin expression, indicating that depletion of human p29 may not affect the post-transcriptional regulation of a-tubulin in human cancer cells. Several DDR- and pre-mRNA splicing-related knockout mice have been investigated. For example, ATM knockout mice are viable, but display growth retardation, infertility, defects in T lymphocyte maturation, and EUK 134 extreme sensitivity to c-irradiation. Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. By contrast, the absence of main players in replication checkpoint results in severely developmental abnormalities.