Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6;129S-Dnmttm1Jae    (Changed: 15-DEC-04 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+4p Generation Definitions   Donating Investigator Dr. Rudolf Jaenisch,   Whitehead Institute (MIT)

Description
Mice homozygous for this mutation die at mid-gestation. The embryos are stunted and show a delayed development. DNA from these mice shows a reduction in the level of m⁵C to about 1/3 that seen in cells from normal wildtype siblings.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Dnmt1^tm1Jae allele

002198

B6.129S4-Dnmt1tm1Jae/J

View Strains carrying   Dnmt1^tm1Jae     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Neuropathy, Hereditary Sensory, Type IE; HSN1E   (DNMT1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Dnmt1^tm1Jae/Dnmt1^tm1Jae

        involves: 129S4/SvJae

• mortality/aging
• complete embryonic lethality
  • die prior to E11   (MGI Ref ID J:1157)
• embryogenesis phenotype
• abnormal embryonic tissue morphology
  • 2/3 of embryos show a structure protruding from the lower abdomen   (MGI Ref ID J:1157)
• abnormal visceral yolk sac morphology
  • small yolk sac   (MGI Ref ID J:1157)
• • pale yolk sac
    • yolk sacs lack visible blood or blood vasculature   (MGI Ref ID J:1157)
• embryonic growth arrest
  • embryos fail to develop beyond the stage characteristic of normal E9.5 embryos   (MGI Ref ID J:1157)
• cellular phenotype
• abnormal DNA methylation
  • total cytosine methylation is about 30% of the level in wild-type   (MGI Ref ID J:1157)
• abnormal imprinting
  • Ifg2 is not expressed due to altered imprinting   (MGI Ref ID J:110857)
• decreased cell proliferation
  • fewer mitotic figures in embryos   (MGI Ref ID J:1157)
• increased apoptosis
  • increase in cell death in embryos   (MGI Ref ID J:1157)
• homeostasis/metabolism phenotype
• abnormal imprinting
  • Ifg2 is not expressed due to altered imprinting   (MGI Ref ID J:110857)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Dnmt1^tm1Jae related

Developmental Biology Research
Embryonic Lethality (Homozygous)

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dnmt1tm1Jae
Allele Name		targeted mutation 1, Rudolf Jaenisch
Allele Type		Targeted (knock-out)
Common Name(s)		Dmntn; Dnmt1N; DnmtN; MTase(-); Mtasen;
Mutation Made By		Dr. Rudolf Jaenisch,   Whitehead Institute (MIT)
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Dnmt1, DNA methyltransferase (cytosine-5) 1
Chromosome		9
Gene Common Name(s)		AIM; CXXC9; DNMT; Dnmt1o; HSN1E; MCMT; MTase; MommeD2; modifier of murine metastable epialleles, D2;
Molecular Note		Replacement of 900 bp, including the translation start site, with a neomycin cassette. This is a hypomorphic allele; enzyme activity levels have dropped to approximately 30% of the normal value. [MGI Ref ID J:1157]

Genotyping

Genotyping Information

Genotyping Protocols

Dnmt1^tm1Jae, Standard PCR
NEOTD (Generic Neo), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Li E; Bestor TH; Jaenisch R. 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69(6):915-26. [PubMed: 1606615]  [MGI Ref ID J:1157]

Additional References

Croteau S; Polychronakos C; Naumova AK. 2001. Imprinting defects in mouse embryos: stochastic errors or polymorphic phenotype? Genesis 31(1):11-6. [PubMed: 11668673]  [MGI Ref ID J:71981]

Li E; Beard C; Forster AC; Bestor TH; Jaenisch R. 1993. DNA methylation, genomic imprinting, and mammalian development. Cold Spring Harb Symp Quant Biol 58:297-305. [PubMed: 7956042]  [MGI Ref ID J:20113]

Dnmt1^tm1Jae related

Bechtel W; McGoohan S; Zeisberg EM; Muller GA; Kalbacher H; Salant DJ; Muller CA; Kalluri R; Zeisberg M. 2010. Methylation determines fibroblast activation and fibrogenesis in the kidney. Nat Med 16(5):544-50. [PubMed: 20418885]  [MGI Ref ID J:160617]

Berger J; Sansom O; Clarke A; Bird A. 2007. MBD2 is required for correct spatial gene expression in the gut. Mol Cell Biol 27(11):4049-57. [PubMed: 17353267]  [MGI Ref ID J:122224]

Chong S; Vickaryous N; Ashe A; Zamudio N; Youngson N; Hemley S; Stopka T; Skoultchi A; Matthews J; Scott HS; de Kretser D; O'Bryan M; Blewitt M; Whitelaw E. 2007. Modifiers of epigenetic reprogramming show paternal effects in the mouse. Nat Genet 39(5):614-22. [PubMed: 17450140]  [MGI Ref ID J:122400]

Cormier RT; Dove WF. 2000. Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele. Cancer Res 60(14):3965-70. [PubMed: 10919675]  [MGI Ref ID J:63662]

Eads CA; Nickel AE; Laird PW. 2002. Complete Genetic Suppression of Polyp Formation and Reduction of CpG-Island Hypermethylation in Apc(Min/+) Dnmt1-Hypomorphic Mice. Cancer Res 62(5):1296-9. [PubMed: 11888894]  [MGI Ref ID J:75230]

Ecke I; Petry F; Rosenberger A; Tauber S; Monkemeyer S; Hess I; Dullin C; Kimmina S; Pirngruber J; Johnsen SA; Uhmann A; Nitzki F; Wojnowski L; Schulz-Schaeffer W; Witt O; Hahn H. 2009. Antitumor effects of a combined 5-aza-2'deoxycytidine and valproic acid treatment on rhabdomyosarcoma and medulloblastoma in Ptch mutant mice. Cancer Res 69(3):887-95. [PubMed: 19155313]  [MGI Ref ID J:144974]

Gonzalo S; Jaco I; Fraga MF; Chen T; Li E; Esteller M; Blasco MA. 2006. DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol 8(4):416-24. [PubMed: 16565708]  [MGI Ref ID J:129529]

Grandjean V; Yaman R; Cuzin F; Rassoulzadegan M. 2007. Inheritance of an Epigenetic Mark: The CpG DNA Methyltransferase 1 Is Required for De Novo Establishment of a Complex Pattern of Non-CpG Methylation. PLoS ONE 2(11):e1136. [PubMed: 17989773]  [MGI Ref ID J:130349]

Hutnick LK; Huang X; Loo TC; Ma Z; Fan G. 2010. Repression of retrotransposal elements in mouse embryonic stem cells is primarily mediated by a DNA methylation-independent mechanism. J Biol Chem 285(27):21082-91. [PubMed: 20404320]  [MGI Ref ID J:165937]

Jones BK; Levorse JM; Tilghman SM. 1998. Igf2 imprinting does not require its own DNA methylation or H19 RNA. Genes Dev 12(14):2200-7. [PubMed: 9679064]  [MGI Ref ID J:110857]

Kinney SR; Moser MT; Pascual M; Greally JM; Foster BA; Karpf AR. 2010. Opposing roles of Dnmt1 in early- and late-stage murine prostate cancer. Mol Cell Biol 30(17):4159-74. [PubMed: 20584988]  [MGI Ref ID J:163289]

Kutay H; Klepper C; Wang B; Hsu SH; Datta J; Yu L; Zhang X; Majumder S; Motiwala T; Khan N; Belury M; McClain C; Jacob S; Ghoshal K. 2012. Reduced susceptibility of DNA methyltransferase 1 hypomorphic (Dnmt1N/+) mice to hepatic steatosis upon feeding liquid alcohol diet. PLoS One 7(8):e41949. [PubMed: 22905112]  [MGI Ref ID J:189908]

Lei H; Oh SP; Okano M; Juttermann R; Goss KA; Jaenisch R; Li E. 1996. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development 122(10):3195-205. [PubMed: 8898232]  [MGI Ref ID J:36234]

Li E; Beard C; Jaenisch R. 1993. Role for DNA methylation in genomic imprinting [see comments] Nature 366(6453):362-5. [PubMed: 8247133]  [MGI Ref ID J:16119]

Maatouk DM; Kellam LD; Mann MR; Lei H; Li E; Bartolomei MS; Resnick JL. 2006. DNA methylation is a primary mechanism for silencing postmigratory primordial germ cell genes in both germ cell and somatic cell lineages. Development 133(17):3411-8. [PubMed: 16887828]  [MGI Ref ID J:112224]

Nan X; Hou J; Maclean A; Nasir J; Lafuente MJ; Shu X; Kriaucionis S; Bird A. 2007. Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation. Proc Natl Acad Sci U S A 104(8):2709-14. [PubMed: 17296936]  [MGI Ref ID J:125897]

Oghamian S; Sodir NM; Bashir MU; Shen H; Cullins AE; Carroll CA; Kundu P; Shibata D; Laird PW. 2011. Reduction of pancreatic acinar cell tumor multiplicity in Dnmt1 hypomorphic mice. Carcinogenesis 32(6):829-35. [PubMed: 21362628]  [MGI Ref ID J:172257]

Schoeftner S; Blasco MA. 2008. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10(2):228-36. [PubMed: 18157120]  [MGI Ref ID J:132362]

Shaknovich R; Cerchietti L; Tsikitas L; Kormaksson M; De S; Figueroa ME; Ballon G; Yang SN; Weinhold N; Reimers M; Clozel T; Luttrop K; Ekstrom TJ; Frank J; Vasanthakumar A; Godley LA; Michor F; Elemento O; Melnick A. 2011. DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation. Blood 118(13):3559-69. [PubMed: 21828137]  [MGI Ref ID J:177061]

Tanaka M; Puchyr M; Gertsenstein M; Harpal K; Jaenisch R; Rossant J; Nagy A. 1999. Parental origin-specific expression of Mash2 is established at the time of implantation with its imprinting mechanism highly resistant to genome-wide demethylation. Mech Dev 87(1-2):129-42. [PubMed: 10495277]  [MGI Ref ID J:57828]

TeKippe M; Harrison DE; Chen J. 2003. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol 31(6):521-7. [PubMed: 12829028]  [MGI Ref ID J:115677]

Trasler JM; Trasler DG; Bestor TH; Li E; Ghibu F. 1996. DNA methyltransferase in normal and Dnmtn/Dnmtn mouse embryos. Dev Dyn 206(3):239-47. [PubMed: 8896980]  [MGI Ref ID J:33741]

Trinh BN; Long TI; Nickel AE; Shibata D; Laird PW. 2002. DNA methyltransferase deficiency modifies cancer susceptibility in mice lacking DNA mismatch repair. Mol Cell Biol 22(9):2906-17. [PubMed: 11940649]  [MGI Ref ID J:75745]

Weaver JR; Sarkisian G; Krapp C; Mager J; Mann MR; Bartolomei MS. 2010. Domain-specific response of imprinted genes to reduced DNMT1. Mol Cell Biol 30(16):3916-28. [PubMed: 20547750]  [MGI Ref ID J:162781]

Yung R; Ray D; Eisenbraun JK; Deng C; Attwood J; Eisenbraun MD; Johnson K; Miller RA; Hanash S; Richardson B. 2001. Unexpected effects of a heterozygous dnmt1 null mutation on age-dependent DNA hypomethylation and autoimmunity. J Gerontol A Biol Sci Med Sci 56(6):B268-76. [PubMed: 11382789]  [MGI Ref ID J:69916]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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