intracisternal a particle genes


Summary: Genes of IAP elements (a family of retrovirus-like genetic elements) which code for virus-like particles (IAPs) found regularly in rodent early embryos. ("Intracisternal" refers to the cisternae of the endoplasmic reticulum.) Under certain circumstances, such as DNA hypomethylation they are transcribed. Their transcripts are found in a variety of neoplasms, including plasmacytomas, neuroblastoma, rhabdomyosarcomas, teratocarcinomas, and colon carcinomas.

Top Publications

  1. Lueders K, Frankel W, Mietz J, Kuff E. Genomic mapping of intracisternal A-particle proviral elements. Mamm Genome. 1993;4:69-77 pubmed
    ..Some of the loci have also been scored in the CXB RI set. The IAP LS loci can provide a significant number of markers with a recognized genetic organization to the mouse genome map. ..
  2. Perry W, Copeland N, Jenkins N. The molecular basis for dominant yellow agouti coat color mutations. Bioessays. 1994;16:705-7 pubmed
    ..Three insertions were identified as intracisternal A-particles, which helps explain the variable coat colors and parental imprinting effects associated with some dominant agouti alleles. ..
  3. Zhang Y, Maksakova I, Gagnier L, van de Lagemaat L, Mager D. Genome-wide assessments reveal extremely high levels of polymorphism of two active families of mouse endogenous retroviral elements. PLoS Genet. 2008;4:e1000007 pubmed publisher
    ..These extreme levels of polymorphism suggest that ERV insertions play a significant role in genetic drift of mouse lines...
  4. Morgan H, Sutherland H, Martin D, Whitelaw E. Epigenetic inheritance at the agouti locus in the mouse. Nat Genet. 1999;23:314-8 pubmed
    ..Because retrotransposons are abundant in mammalian genomes, this type of inheritance may be common. ..
  5. Dupressoir A, Barbot W, Loireau M, Heidmann T. Characterization of a mammalian gene related to the yeast CCR4 general transcription factor and revealed by transposon insertion. J Biol Chem. 1999;274:31068-75 pubmed
    ..The strong amino acid conservation between the human, murine, and the previously identified Xenopus CCR4-like proteins, is consistent with an important and conserved role for this protein in vertebrates. ..
  6. Walsh C, Chaillet J, Bestor T. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat Genet. 1998;20:116-7 pubmed
  7. Ishihara H, Tanaka I. Detection and cloning of unique integration sites of retrotransposon, intracisternal A-particle element in the genome of acute myeloid leukemia cells in mice. FEBS Lett. 1997;418:205-9 pubmed
    ..The data suggest that IAP-mediated retrotransposition occurs frequently in radiation-induced AML cells from C3H/He mice...
  8. Puech A, Dupressoir A, Loireau M, Mattei M, Heidmann T. Characterization of two age-induced intracisternal A-particle-related transcripts in the mouse liver. Transcriptional read-through into an open reading frame with similarities to the yeast ccr4 transcription factor. J Biol Chem. 1997;272:5995-6003 pubmed
    ..Characterization of this locus should now allow studies on its chromatin and methylation status, and on the "molecular factors of senescence" possibly involved in its induction. ..
  9. Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J, et al. Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis. 2003;35:88-93 pubmed
    ..In turn, this can result in the transgenerational inheritance of epigenetic states of IAPs, which could lead to heritable epimutations of neighbouring genes through influencing their transcriptional states. ..

More Information


  1. Kantheti P, Diaz M, Peden A, Seong E, Dolan D, Robinson M, et al. Genetic and phenotypic analysis of the mouse mutant mh2J, an Ap3d allele caused by IAP element insertion. Mamm Genome. 2003;14:157-67 pubmed
  2. Argeson A, Nelson K, Siracusa L. Molecular basis of the pleiotropic phenotype of mice carrying the hypervariable yellow (Ahvy) mutation at the agouti locus. Genetics. 1996;142:557-67 pubmed
    ..In addition, the data suggest that the variable phenotype of Ahvy offspring is influenced in part by the phenotype of their Ahvy female parent. ..
  3. Zolotukhin A, Schneider R, Uranishi H, Bear J, Tretyakova I, Michalowski D, et al. The RNA transport element RTE is essential for IAP LTR-retrotransposon mobility. Virology. 2008;377:88-99 pubmed publisher
    ..These data reveal that, despite a complex evolutionary history, retroelements and retroviruses share the dependency on posttranscriptional regulation. ..
  4. Horie K, Saito E, Keng V, Ikeda R, Ishihara H, Takeda J. Retrotransposons influence the mouse transcriptome: implication for the divergence of genetic traits. Genetics. 2007;176:815-27 pubmed
    ..On the basis of these data, we propose that retrotransposons are one of the drivers that shape the mammalian transcriptome. ..
  5. Stocking C, Kozak C. Murine endogenous retroviruses. Cell Mol Life Sci. 2008;65:3383-98 pubmed publisher
    ..We review mechanisms by which an adaptive coexistence has evolved. (Part of a multi-author review)...
  6. Sugita T, Totsuka T, Saito M, Yamasaki K, Taga T, Hirano T, et al. Functional murine interleukin 6 receptor with the intracisternal A particle gene product at its cytoplasmic domain. Its possible role in plasmacytomagenesis. J Exp Med. 1990;171:2001-9 pubmed
    ..Since IL-6 functions as a potent growth factor for murine plasmacytomas, over-expression of abnormal IL-6-R may function as a positive selection element for the development of certain plasmacytomas. ..
  7. Bogerd H, Wiegand H, Doehle B, Lueders K, Cullen B. APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in human cells. Nucleic Acids Res. 2006;34:89-95 pubmed
    ..Moreover, these results argue that APOBEC3A inhibits IAP retrotransposition via a novel mechanism that is distinct from, and in this case more effective than, the DNA editing mechanism characteristic of APOBEC3G and APOBEC3B. ..
  8. Ishihara H, Tanaka I, Wan H, Nojima K, Yoshida K. Retrotransposition of limited deletion type of intracisternal A-particle elements in the myeloid leukemia Clls of C3H/He mice. J Radiat Res. 2004;45:25-32 pubmed
    ..This indicates that limited populations of the IAP elements contribute to the unique retrotransposition in AML cells...
  9. Poznanski A, Calarco P. The expression of intracisternal A particle genes in the preimplantation mouse embryo. Dev Biol. 1991;143:271-81 pubmed
    ..The presence of type I, II, and p73 in the unfertilized egg strongly suggests maternal inheritance from the oocyte. ..
  10. Leslie K, Lee F, Schrader J. Intracisternal A-type particle-mediated activations of cytokine genes in a murine myelomonocytic leukemia: generation of functional cytokine mRNAs by retroviral splicing events. Mol Cell Biol. 1991;11:5562-70 pubmed
    ..The functional IL-3 and GM-CSF mRNAs were generated by mechanisms in which the splice donor apparatus of the IAP sequence has been used in IAP gag-to-IL-3 or -GM-CSF splicing events. ..
  11. Lueders K, Frankel W. Mapping of mouse intracisternal A-particle proviral markers in an interspecific backcross. Mamm Genome. 1994;5:473-8 pubmed
    ..The mapped IAP loci were widely dispersed on the X Chromosome (Chr) and all of the autosomes except Chrs 9 and 19, providing useful genetic markers for linkage studies. ..
  12. Svoboda P, Stein P, Anger M, Bernstein E, Hannon G, Schultz R. RNAi and expression of retrotransposons MuERV-L and IAP in preimplantation mouse embryos. Dev Biol. 2004;269:276-85 pubmed
  13. Qin C, Wang Z, Shang J, Bekkari K, Liu R, Pacchione S, et al. Intracisternal A particle genes: Distribution in the mouse genome, active subtypes, and potential roles as species-specific mediators of susceptibility to cancer. Mol Carcinog. 2010;49:54-67 pubmed publisher
    ..This systemic analysis provides a solid foundation for further investigations of the role of IAPs as species- and strain-specific disease susceptibility factors...
  14. Michaud E, van Vugt M, Bultman S, Sweet H, Davisson M, Woychik R. Differential expression of a new dominant agouti allele (Aiapy) is correlated with methylation state and is influenced by parental lineage. Genes Dev. 1994;8:1463-72 pubmed
  15. Tanaka I, Ishihara H. Unusual long target duplication by insertion of intracisternal A-particle element in radiation-induced acute myeloid leukemia cells in mouse. FEBS Lett. 1995;376:146-50 pubmed
    ..This suggests the possibility of a radiation-induced integration mechanism which is distinct from normal retrotransmission...
  16. Blankenstein T, Qin Z, Li W, Diamantstein T. DNA rearrangement and constitutive expression of the interleukin 6 gene in a mouse plasmacytoma. J Exp Med. 1990;171:965-70 pubmed
    ..The IL-6 gene is constitutively expressed in MPC11, suggesting the involvement of IL-6 in the development of certain myeloma/plasmacytomas according to the "autocrine growth hypothesis". ..
  17. Ribet D, Harper F, Dupressoir A, Dewannieux M, Pierron G, Heidmann T. An infectious progenitor for the murine IAP retrotransposon: emergence of an intracellular genetic parasite from an ancient retrovirus. Genome Res. 2008;18:597-609 pubmed publisher
  18. Chang Yeh A, Mold D, Brilliant M, Huang R. The mouse intracisternal A particle-promoted placental gene retrotransposition is mouse-strain-specific. Proc Natl Acad Sci U S A. 1993;90:292-6 pubmed
    ..The symbol Ipp is being used for this gene in all major mouse data bases and in the comparative section of the human genome data base. ..
  19. Dewannieux M, Dupressoir A, Harper F, Pierron G, Heidmann T. Identification of autonomous IAP LTR retrotransposons mobile in mammalian cells. Nat Genet. 2004;36:534-9 pubmed
    ..Their high rates of retrotransposition indicate that they are potent insertional mutagens that could serve as safe (noninfectious) genetic tools in a large panel of cells. ..
  20. Gaudet F, Rideout W, Meissner A, Dausman J, Leonhardt H, Jaenisch R. Dnmt1 expression in pre- and postimplantation embryogenesis and the maintenance of IAP silencing. Mol Cell Biol. 2004;24:1640-8 pubmed
  21. Sun X, Chen Z, Hayashi Y, Kanou Y, Takagishi Y, Oda S, et al. Insertion of an intracisternal A particle retrotransposon element in plasma membrane calcium ATPase 2 gene attenuates its expression and produces an ataxic phenotype in joggle mutant mice. Gene. 2008;411:94-102 pubmed publisher
    ..Thus, we attributed ataxia in joggle mice to reduced expression of Pmca2, resulting from insertion of the IAP element. ..
  22. Sander D, Wolfsheimer K, Gallaher W, Fermin C, Haislip A, Garry R. Seroreactivity to A-type retrovirus proteins in a subset of cats with hyperthyroidism. Microsc Res Tech. 2005;68:235-8 pubmed
    ..These results suggest that it may be possible to develop an animal (feline) model for the role of retroviruses in thyroid autoimmune diseases. ..
  23. Tanaka I, Ishihara H. Enhanced expression of the early retrotransposon in C3H mouse-derived myeloid leukemia cells. Virology. 2001;280:107-14 pubmed
    ..The overexpression of ETn as a common phenotype of AML cells suggests that myeloid cells with this phenotype are the origin of all the AML cells or that the phenotype is acquired during leukemogenesis. ..
  24. Braun E, Rorman E, Lueders K, Bar Sinai A, Hochman J. Differential expression of intracisternal A-particle transcripts in immunogenic versus tumorigenic S49 murine lymphoma cells. Virology. 2000;277:136-46 pubmed
    ..These findings suggest that, in the S49 lymphoma, selectively expressed IAP retroviral elements may function in a tumor suppressive capacity by affecting the immunogenic potential of these cells. ..
  25. Royaux I, Bernier B, Montgomery J, Flaherty L, Goffinet A. Reln(rl-Alb2), an allele of reeler isolated from a chlorambucil screen, is due to an IAP insertion with exon skipping. Genomics. 1997;42:479-82 pubmed
    ..At the genomic level, the mutation was shown to be due to an intracisternal A-particle insertion leading to exon skipping. This appears to be the first observation of retrotransposon insertion during chlorambucil mutagenesis. ..
  26. Wu M, Rinchik E, Wilkinson E, Johnson D. Inherited somatic mosaicism caused by an intracisternal A particle insertion in the mouse tyrosinase gene. Proc Natl Acad Sci U S A. 1997;94:890-4 pubmed
    ..We propose that the IAP insertion isolates the promoter of the tyrosinase gene from upstream cis-acting regulatory elements, leading to a substantially decreased level of Tyr gene expression in mutants. ..
  27. Esnault C, Priet S, Ribet D, Heidmann O, Heidmann T. Restriction by APOBEC3 proteins of endogenous retroviruses with an extracellular life cycle: ex vivo effects and in vivo "traces" on the murine IAPE and human HERV-K elements. Retrovirology. 2008;5:75 pubmed publisher
  28. Motáčková V, Kubícková M, Kozísek M, Sasková K, Svec M, Zídek L, et al. Backbone (1)H, (13)C, and (15)N NMR assignment for the inactive form of the retroviral protease of the murine intracisternal A-type particle, inMIA-14 PR. Biomol NMR Assign. 2009;3:261-4 pubmed publisher
    ..An almost complete assignments of the main chain and (13)C(beta) side chain resonances of the 34 kDa homo-dimeric inMIA-14 PR is presented in this study. ..
  29. Lueders K, Grossman Z, Fewell J. Characterization of amplified intracisternal A-particle elements encoding integrase. Nucleic Acids Res. 1989;17:9267-77 pubmed
  30. Galien R, Mercier G, Garcette M, Emanoil Ravier R. ras oncogene activates the intracisternal A particle long terminal repeat promoter through a c-AMP response element. Oncogene. 1991;6:849-55 pubmed
    ..CAT assays demonstrate that the ras responsive sequence is a 16 bp oligonucleotide containing an effective c-AMP Response Element (CRE) TGACGTCA, which is located in the U3 region, 20 bp upstream of the CAAT box...
  31. Brigle K, Westin E, Houghton M, Goldman I. Insertion of an intracisternal A particle within the 5'-regulatory region of a gene encoding folate-binding protein in L1210 leukemia cells in response to low folate selection. Association with increased protein expression. J Biol Chem. 1992;267:22351-5 pubmed
    ..Presence of the IAP appears to inactivate or relocate normal cis-acting regulatory sequences as expression of the FBP1 transcript in LL1 is not regulated by the folate status of the cell. ..
  32. Saito E, Keng V, Takeda J, Horie K. Translation from nonautonomous type IAP retrotransposon is a critical determinant of transposition activity: implication for retrotransposon-mediated genome evolution. Genome Res. 2008;18:859-68 pubmed publisher
    ..The active role of the nonautonomous type IAP protein revealed in this study may provide a new insight into retrotransposon proliferation within the genome. ..
  33. Hasel C, Bhanot U, Maier R, Strater J, Moller P. [Parenchymal regression in chronic pancreatitis spares islets reprogrammed for expression of NFkappaB and IAPs]. Verh Dtsch Ges Pathol. 2006;90:159-67 pubmed
    ..They also neo-express NFkappaB subunits, survivin, and cIAP1. This apoptosis-inhibitory security program might be enforced by PSC-derived TRAIL. ..
  34. Morita S, Horii T, Kimura M, Goto Y, Ochiya T, Hatada I. One Argonaute family member, Eif2c2 (Ago2), is essential for development and appears not to be involved in DNA methylation. Genomics. 2007;89:687-96 pubmed
    ..This suggests that developmental defects in the Eif2c2-deficient mouse are caused not at the transcriptional level, but rather at the posttranscriptional level through the miRNA-protein complex. ..
  35. Rowe H, Jakobsson J, Mesnard D, Rougemont J, Reynard S, Aktas T, et al. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature. 2010;463:237-40 pubmed publisher
    ..Correspondingly, IAP 5'UTR sequences can impose in cis KAP1-dependent repression on a heterologous promoter in ES cells. Our results establish that KAP1 controls endogenous retroelements during early embryonic development. ..
  36. Sander D, Szabo S, Gallaher W, Deas J, Thompson J, Cao Y, et al. Involvement of human intracisternal A-type retroviral particles in autoimmunity. Microsc Res Tech. 2005;68:222-34 pubmed
    ..Additionally, results of comprehensive surveys of autoimmune patients to determine seroreactivity to HIAP, and other human retroviruses, including HIV and human T-lymphotropic virus type I, are reported. ..
  37. Jiao Y, Jin X, Yan J, Jiao F, Li X, Roe B, et al. An insertion of intracisternal A-particle retrotransposon in a novel member of the phosphoglycerate mutase family in the lew allele of mutant mice. Genes Genet Syst. 2009;84:327-34 pubmed
  38. Aurelian L. Cross talk of signaling and apoptotic cascades in the CNS: target for virus modulation. Front Biosci. 2005;10:2776-87 pubmed
    ..All are targets of virus modulation. These cascades are briefly described in this review, underscoring cross talk and the integration of distinct signals that contribute to central nervous system (CNS) disease. ..
  39. Yamamoto M, Hashimoto H, Tachibana T, Ohi S, Akahori M, Yokose T, et al. New method for forming large embryoid bodies using the wall of the culture dish along with an analysis of their structural characteristics. Hum Cell. 2004;17:49-57 pubmed
  40. Lucifero D, Mann M, Bartolomei M, Trasler J. Gene-specific timing and epigenetic memory in oocyte imprinting. Hum Mol Genet. 2004;13:839-49 pubmed
    ..These findings contribute to our understanding of the epigenetic mechanisms underlying imprint acquisition during female germ cell development and have implications for the practice of assisted reproductive technologies. ..
  41. Schütt S, Florl A, Shi W, Hemberger M, Orth A, Otto S, et al. DNA methylation in placentas of interspecies mouse hybrids. Genetics. 2003;165:223-8 pubmed
    ..Thus, our results strongly suggest that generalized changes in methylation patterns do not occur in trophoblast cells of such hybrids. ..
  42. Fehrmann F, Jung M, Zimmermann R, Kräusslich H. Transport of the intracisternal A-type particle Gag polyprotein to the endoplasmic reticulum is mediated by the signal recognition particle. J Virol. 2003;77:6293-304 pubmed
  43. Wodrich H, Bohne J, Gumz E, Welker R, Krausslich H. A new RNA element located in the coding region of a murine endogenous retrovirus can functionally replace the Rev/Rev-responsive element system in human immunodeficiency virus type 1 Gag expression. J Virol. 2001;75:10670-82 pubmed
    ..There was no overall homology between the IAPE and the CTE, but there was complete sequence identity between short putative single-stranded loops. Deletion of these loops from the IAPE severely reduced Rev-independent Gag expression. ..
  44. Reed J. Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med. 2001;7:314-9 pubmed
  45. Forsell P, Boie Y, Montalibet J, Collins S, Kennedy B. Genomic characterization of the human and mouse protein tyrosine phosphatase-1B genes. Gene. 2000;260:145-53 pubmed
    ..In addition, the promoter in a number of mouse strains contains, 3.5 kb upstream of the start codon, an insertion of an intracisternal a particle (IAP) element that possibly could alter the expression of PTP-1B mRNA in these strains. ..
  46. Tabernero C, Zolotukhin A, Bear J, Schneider R, Karsenty G, Felber B. Identification of an RNA sequence within an intracisternal-A particle element able to replace Rev-mediated posttranscriptional regulation of human immunodeficiency virus type 1. J Virol. 1997;71:95-101 pubmed
    ..These findings suggest that such elements may be involved in posttranscriptional regulation of cellular mRNAs. ..
  47. Urnovitz H, Murphy W. Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease. Clin Microbiol Rev. 1996;9:72-99 pubmed
    ..The current major needs are to improve methods for HERV detection, to identify the most appropriate HERV prototypes, and to develop diagnostic reagents so that the putative biologic and pathologic roles of HERVs can be better evaluated. ..
  48. Algate P, McCubrey J. Autocrine transformation of hemopoietic cells resulting from cytokine message stabilization after intracisternal A particle transposition. Oncogene. 1993;8:1221-32 pubmed
    ..Therefore, IAP proviral transposition can activate IL-3 gene expression by prolonging mRNA stability, and this mechanism can contribute to the autocrine transformation of the hemopoietic cells. ..
  49. Lueders K, Fewell J, Morozov V, Kuff E. Selective expression of intracisternal A-particle genes in established mouse plasmacytomas. Mol Cell Biol. 1993;13:7439-46 pubmed
    ..Overall, the results show that established plasmacytomas exhibit a characteristic pattern of IAP proviral hypomethylation and regulatory sequence selection. ..
  50. Lueders K. Differences in intracisternal A-particle and GLN proviral loci suggest a genetic contribution from a DBA/2-like strain in generation of the C57BL/Ks strain. Mamm Genome. 1995;6:134-6 pubmed
  51. Ymer S, Tucker W, Campbell H, Young I. Nucleotide sequence of the intracisternal A-particle genome inserted 5' to the interleukin-3 gene of the leukemia cell line WEHI-3B. Nucleic Acids Res. 1986;14:5901-18 pubmed
    ..Comparison between the pol region of IAP-IL3 and other retroviruses suggests that IAP-IL3 is most closely related to type B and type D retroviruses. ..
  52. Mold D, Chang Yeh A, Huang R. Cell lineage-specific expression of the MIPP gene. Biochem Biophys Res Commun. 1991;177:1062-7 pubmed
    ..The expression of IAP genes paralleled that of MIPP in all tissues studied except for the presence of IAP transcripts in the amnion. ..
  53. Ben David L, Aberdam D, Sachs L, Blatt C. A deletion and a rearrangement distinguish between the intracisternal A-particle of Hox-2.4 and that of interleukin-3 in the same leukemic cells. Virology. 1991;182:382-7 pubmed
    ..Both proviral insertions have resulted in transcriptional activation of the adjacent genes, which appears to be a significant step in the leukemogenic process in these leukemic cells. ..