title: Disruption of murine mp29/Syf2/Ntc31 gene results in embryonic lethality with aberrant checkpoint response.
abstract: Human p29 is a putative component of spliceosomes, but its role in pre-mRNA is elusive. By siRNA knockdown and stable overexpression, we demonstrated that human p29 is involved in DNA damage response and Fanconi anemia pathway in cultured cells. In this study, we generated p29 knockout mice (mp29(GT/GT)) using the mp29 gene trap embryonic stem cells to study the role of mp29 in DNA damage response in vivo. Interruption of mp29 at both alleles resulted in embryonic lethality. Embryonic abnormality occurred as early as E6.5 in mp29(GT/GT) mice accompanied with decreased mRNA levels of α-tubulin and Chk1. The reduction of α-tubulin and Chk1 mRNAs is likely due to an impaired post-transcriptional event. An aberrant G2/M checkpoint was found in mp29 gene trap embryos when exposed to aphidicolin and UV light. This embryonic lethality was rescued by crossing with mp29 transgenic mice. Additionally, the knockdown of zfp29 in zebrafish resulted in embryonic death at 72 hours of development postfertilization (hpf). A lower level of acetylated α-tubulin was also observed in zfp29 morphants. Together, these results illustrate an indispensable role of mp29 in DNA checkpoint response during embryonic development.
authors.affiliation: Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Chen
authors.forename: Po-Chen
authors.initials: PC
authors.lastname: Chu
authors.forename: Liekyeow
authors.initials: L
authors.lastname: Lee
authors.forename: Huang-Wei
authors.initials: HW
authors.lastname: Lien
authors.forename: Tse-Ling
authors.initials: TL
authors.lastname: Lin
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Fan
authors.forename: Peter
authors.initials: P
authors.lastname: Chi
authors.forename: Chang-Jen
authors.initials: CJ
authors.lastname: Huang
authors.forename: Mau-Sun
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000473:pathology*; D004625:Embryo, Nonmammalian / Q000473:pathology*; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D005816:Genetic Complementation Test; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C469943:Gcipip protein, mouse; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014404:Tubulin; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse