Ddx1 Knockout Results in Transgenerational Wild-type Lethality in Mice

Overview

Journal Sci Rep

Specialty Science

Date 2015 Apr 25

PMID 25909345

Citations 12

Authors

Matthew R Hildebrandt

Devon R Germain

Elizabeth A Monckton

Miranda Brun

Roseline Godbout

Affiliations

Soon will be listed here.

Abstract

DEAD box 1 (DDX1) is a member of the DEAD box family of RNA helicases which are involved in all aspects of RNA metabolism. DDX1 has been implicated in a variety of biological processes, including 3'-end processing of mRNA, DNA repair, microRNA processing, tRNA maturation and mRNA transport. To study the role of DDX1 during development, we have generated mice carrying a constitutive Ddx1 knock-out allele. Ddx1(+/-) mice have no obvious phenotype and express similar levels of DDX1 as wild-type mice indicating compensation from the intact Ddx1 allele. Heterozygote matings produce no viable Ddx1(-/-) progeny, with Ddx1(-/-) embryos dying prior to embryonic day (E) 3.5. Intriguingly, the number of wild-type progeny is significantly decreased in heterozygote crosses, with two different heterozygote populations identified based on parental genotype: (i) normal Ddx1(+/-) mice which generate the expected number of wild-type progeny and (ii) Ddx1*(/-) mice (with * signifying a non-genetically altered allele) which generate a significantly reduced number of wild-type mice. The transgenerational inheritance of wild-type lethality observed upon crossing Ddx1*(/-) mice is independent of parental sex and occurs in cis through a mechanism that is different from other types of previously reported transgenerational epigenetic inheritance.

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References

Rohde C, Zhang Y, Reinhardt R, Jeltsch A . BISMA--fast and accurate bisulfite sequencing data analysis of individual clones from unique and repetitive sequences. BMC Bioinformatics. 2010; 11:230. PMC: 2877691. DOI: 10.1186/1471-2105-11-230. View

Inoue A, Li T, Roby S, Valentine M, Inoue M, Boyd K . Loss of ChlR1 helicase in mouse causes lethality due to the accumulation of aneuploid cells generated by cohesion defects and placental malformation. Cell Cycle. 2007; 6(13):1646-54. DOI: 10.4161/cc.6.13.4411. View

Li L, Dahiya R . MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002; 18(11):1427-31. DOI: 10.1093/bioinformatics/18.11.1427. View

Lamm G, Nicol S, Fuller-Pace F, Lamond A . p72: a human nuclear DEAD box protein highly related to p68. Nucleic Acids Res. 1996; 24(19):3739-47. PMC: 146168. DOI: 10.1093/nar/24.19.3739. View

George R, Kenyon R, McGuckin A, Malcolm A, Pearson A, Lunec J . Investigation of co-amplification of the candidate genes ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box gene, DDX1, with N-myc in neuroblastoma. United Kingdom Children's Cancer Study Group. Oncogene. 1996; 12(7):1583-7. View

Cuzin F, Rassoulzadegan M . Non-Mendelian epigenetic heredity: gametic RNAs as epigenetic regulators and transgenerational signals. Essays Biochem. 2010; 48(1):101-6. DOI: 10.1042/bse0480101. View

Popow J, Englert M, Weitzer S, Schleiffer A, Mierzwa B, Mechtler K . HSPC117 is the essential subunit of a human tRNA splicing ligase complex. Science. 2011; 331(6018):760-4. DOI: 10.1126/science.1197847. View

Han C, Liu Y, Wan G, Choi H, Zhao L, Ivan C . The RNA-binding protein DDX1 promotes primary microRNA maturation and inhibits ovarian tumor progression. Cell Rep. 2014; 8(5):1447-60. PMC: 4163106. DOI: 10.1016/j.celrep.2014.07.058. View

Bleoo S, Sun X, Hendzel M, Rowe J, Packer M, Godbout R . Association of human DEAD box protein DDX1 with a cleavage stimulation factor involved in 3'-end processing of pre-MRNA. Mol Biol Cell. 2001; 12(10):3046-59. PMC: 60154. DOI: 10.1091/mbc.12.10.3046. View

10.

Squire J, Thorner P, Weitzman S, Maggi J, Dirks P, Doyle J . Co-amplification of MYCN and a DEAD box gene (DDX1) in primary neuroblastoma. Oncogene. 1995; 10(7):1417-22. View

11.

Tsai-Morris C, Sheng Y, Lee E, Lei K, Dufau M . Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is essential for spermatid development and completion of spermatogenesis. Proc Natl Acad Sci U S A. 2004; 101(17):6373-8. PMC: 404052. DOI: 10.1073/pnas.0401855101. View

12.

Weber A, Imisch P, Bergmann E, Christiansen H . Coamplification of DDX1 correlates with an improved survival probability in children with MYCN-amplified human neuroblastoma. J Clin Oncol. 2004; 22(13):2681-90. DOI: 10.1200/JCO.2004.07.192. View

13.

Grandjean V, Gounon P, Wagner N, Martin L, Wagner K, Bernex F . The miR-124-Sox9 paramutation: RNA-mediated epigenetic control of embryonic and adult growth. Development. 2009; 136(21):3647-55. DOI: 10.1242/dev.041061. View

14.

Li L, Roy K, Katyal S, Sun X, Bleoo S, Godbout R . Dynamic nature of cleavage bodies and their spatial relationship to DDX1 bodies, Cajal bodies, and gems. Mol Biol Cell. 2005; 17(3):1126-40. PMC: 1382303. DOI: 10.1091/mbc.e05-08-0768. View

15.

Onishi H, Kino Y, Morita T, Futai E, Sasagawa N, Ishiura S . MBNL1 associates with YB-1 in cytoplasmic stress granules. J Neurosci Res. 2008; 86(9):1994-2002. DOI: 10.1002/jnr.21655. View

16.

Li L, Monckton E, Godbout R . A role for DEAD box 1 at DNA double-strand breaks. Mol Cell Biol. 2008; 28(20):6413-25. PMC: 2577411. DOI: 10.1128/MCB.01053-08. View

17.

Fuller-Pace F . RNA helicases: modulators of RNA structure. Trends Cell Biol. 1994; 4(8):271-4. DOI: 10.1016/0962-8924(94)90210-0. View

18.

Mallona I, Diez-Villanueva A, Peinado M . Methylation plotter: a web tool for dynamic visualization of DNA methylation data. Source Code Biol Med. 2014; 9:11. PMC: 4066318. DOI: 10.1186/1751-0473-9-11. View

19.

Godbout R, Packer M, Katyal S, Bleoo S . Cloning and expression analysis of the chicken DEAD box gene DDX1. Biochim Biophys Acta. 2002; 1574(1):63-71. DOI: 10.1016/s0167-4781(01)00346-3. View

20.

Manohar C, Salwen H, Brodeur G, Cohn S . Co-amplification and concomitant high levels of expression of a DEAD box gene with MYCN in human neuroblastoma. Genes Chromosomes Cancer. 1995; 14(3):196-203. DOI: 10.1002/gcc.2870140307. View