Strain Name:

B6.129S6-Dnmt3ltm1Bes/J

Stock Number:

004267

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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

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Timothy H. Bestor,   Columbia University

Description
Mice that are homozygous for this targeted allele are viable, normal in size, do not display any gross physical or behavioral abnormalities, but are sterile. Adult homozygous males display severe hypogonadism, Sertoli-cell-only phenotype and apoptotic death of spermatocytes prior to pachytene with loss of spermatogonia progressing to nonsyndromic azoospermia in later adulthood. Extreme abnormalities of meitotic pairing occur. There is a failure to methylate transposons in prospermatogonia with expression of very high levels of both LTR and non-LTR transposons in spermatogonia and spermatocytes. Homozygous females have normal oogenesis. Heterozygous progeny of homozygous females do not develop past 9.5 day post coitum, with pericardial edema with exencephaly and other neural tube defects. Maternally imprinted gene sequence that is usually heavily methylated in control oocytes is undermethylated in mutant mice oocytes. Paternally imprinted gene sequence is not effected and global genome methylation is not reduced in heterozygous progeny of homozygous females. This mutant mouse strain represents a model that may be useful in studies of genomic imprinting and cloning.

Development
A targeting vector containing Beta-galactosidase- neomycin phosphotransferase fusion gene (beta-geo) driven by the endogenous Dnmt3l promoter was used to disupt exons 2-5. The construct was transfected into 129S6/SvEvTac derived CSL3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were backcrossed to B6;129 mice.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Dnmt3ltm1Bes/Dnmt3ltm1Bes

        involves: 129S6/SvEvTac
  • mortality/aging
  • complete prenatal lethality
    • no viable pups are recovered at birth from homozygous females   (MGI Ref ID J:73452)
  • cardiovascular system phenotype
  • pericardial edema
    • pericardial edema is seen in embryos from homozygous females   (MGI Ref ID J:73452)
  • embryogenesis phenotype
  • abnormal chorion morphology   (MGI Ref ID J:73452)
  • abnormal ectoplacental cone morphology
    • excess maternal blood is found near the ectoplacental cone in embryos from homozygous females   (MGI Ref ID J:73452)
  • abnormal trophoblast layer morphology
    • the secondary trophoblastic giant cells hyperproliferate resulting in overgrowth of the chorion that is seen in embryos from homozygous females   (MGI Ref ID J:73452)
    • increased trophoblast giant cell number
      • the secondary trophoblastic giant cells hyperproliferate   (MGI Ref ID J:73452)
  • abnormal visceral yolk sac morphology
    • hyperproliferation of the yolk sac endoderm is seen in embryos from homozygous females   (MGI Ref ID J:73452)
  • failure of chorioallantoic fusion
    • the chorioallantoic fusion fails in embryos from homozygous females   (MGI Ref ID J:73452)
  • endocrine/exocrine gland phenotype
  • small testis
    • adult males have severe hypogonadism   (MGI Ref ID J:73452)
  • homeostasis/metabolism phenotype
  • pericardial edema
    • pericardial edema is seen in embryos from homozygous females   (MGI Ref ID J:73452)
  • reproductive system phenotype
  • abnormal oogenesis
    • failure of maternal methylated gene imprinting is seen in homozygous females   (MGI Ref ID J:73452)
  • abnormal spermatogenesis
    • delayed entry of germ cells into meiosis, as indicated by a lower frequency of tubules containing gamma-H2AX positive cells in 10-day old males   (MGI Ref ID J:128710)
    • male germ cells exhibit abnormal methylation of paternally imprinted genes   (MGI Ref ID J:128710)
    • azoospermia
      • seminiferous tubules contain only Sertoli cells   (MGI Ref ID J:73452)
  • decreased male germ cell number
    • by P10, males have about a quarter of the number of germ cells as heterozygous littermates   (MGI Ref ID J:128710)
    • azoospermia
      • seminiferous tubules contain only Sertoli cells   (MGI Ref ID J:73452)
  • infertility
    • both sexes are sterile   (MGI Ref ID J:73452)
    • female infertility   (MGI Ref ID J:73452)
    • male infertility   (MGI Ref ID J:73452)
  • small testis
    • adult males have severe hypogonadism   (MGI Ref ID J:73452)
  • nervous system phenotype
  • exencephaly
    • exencephaly and other neural tube defects are seen in embryos from homozygous females   (MGI Ref ID J:73452)
View Research Applications

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

Dnmt3ltm1Bes related

Developmental Biology Research
Internal/Organ Defects
      heart
Neural Tube Defects

Reproductive Biology Research
Developmental Defects Affecting Gonads
Fertility Defects

Research Tools
Reproductive Biology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Dnmt3ltm1Bes
Allele Name targeted mutation 1, Timothy Bestor
Allele Type Targeted (Reporter)
Common Name(s) Dmnt3lG;
Mutation Made By Timothy Bestor,   Columbia University
Strain of Origin129S6/SvEvTac
ES Cell Line NameCSL3
ES Cell Line Strain129S6/SvEvTac
Gene Symbol and Name Dnmt3l, DNA (cytosine-5-)-methyltransferase 3-like
Chromosome 10
Gene Common Name(s) D6Ertd14e; DNA segment, Chr 6, ERATO Doi 14, expressed; ecat7;
Molecular Note A genomic fragment containing four exons was replaced with an in frame beta-galactosidase-neomycin (beta-geo) fusion gene. A fusion protein is expressed under the contol of the endogenous gene promoter. [MGI Ref ID J:73452]

Genotyping

Genotyping Information

Genotyping Protocols

Dnmt31tm1Bes, Standard PCR
NEOTD (Generic Neo), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bourc'his D; Xu GL; Lin CS; Bollman B; Bestor TH. 2001. Dnmt3L and the establishment of maternal genomic imprints. Science 294(5551):2536-9. [PubMed: 11719692]  [MGI Ref ID J:73452]

Additional References

Dnmt3ltm1Bes related

Aravin AA; Sachidanandam R; Bourc'his D; Schaefer C; Pezic D; Toth KF; Bestor T; Hannon GJ. 2008. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell 31(6):785-99. [PubMed: 18922463]  [MGI Ref ID J:141096]

Bourc'his D; Bestor TH. 2004. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431(7004):96-9. [PubMed: 15318244]  [MGI Ref ID J:92661]

Guenatri M; Duffie R; Iranzo J; Fauque P; Bourc'his D. 2013. Plasticity in Dnmt3L-dependent and -independent modes of de novo methylation in the developing mouse embryo. Development 140(3):562-72. [PubMed: 23293288]  [MGI Ref ID J:194075]

Iglesias-Platas I; Martin-Trujillo A; Cirillo D; Court F; Guillaumet-Adkins A; Camprubi C; Bourc'his D; Hata K; Feil R; Tartaglia G; Arnaud P; Monk D. 2012. Characterization of novel paternal ncRNAs at the Plagl1 locus, including Hymai, predicted to interact with regulators of active chromatin. PLoS One 7(6):e38907. [PubMed: 22723905]  [MGI Ref ID J:187821]

La Salle S; Oakes CC; Neaga OR; Bourc'his D; Bestor TH; Trasler JM. 2007. Loss of spermatogonia and wide-spread DNA methylation defects in newborn male mice deficient in DNMT3L. BMC Dev Biol 7(1):104. [PubMed: 17875220]  [MGI Ref ID J:128710]

Lee DH; Singh P; Tsai SY; Oates N; Spalla A; Spalla C; Brown L; Rivas G; Larson G; Rauch TA; Pfeifer GP; Szabo PE. 2010. CTCF-dependent chromatin bias constitutes transient epigenetic memory of the mother at the H19-Igf2 imprinting control region in prospermatogonia. PLoS Genet 6(11):e1001224. [PubMed: 21124827]  [MGI Ref ID J:167515]

Mahadevaiah SK; Bourc'his D; de Rooij DG; Bestor TH; Turner JM; Burgoyne PS. 2008. Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation. J Cell Biol 182(2):263-76. [PubMed: 18663141]  [MGI Ref ID J:139518]

Menheniott TR; Woodfine K; Schulz R; Wood AJ; Monk D; Giraud AS; Baldwin HS; Moore GE; Oakey RJ. 2008. Genomic imprinting of Dopa decarboxylase in heart and reciprocal allelic expression with neighboring Grb10. Mol Cell Biol 28(1):386-96. [PubMed: 17967881]  [MGI Ref ID J:128957]

Monk D; Wagschal A; Arnaud P; Muller PS; Parker-Katiraee L; Bourc'his D; Scherer SW; Feil R; Stanier P; Moore GE. 2008. Comparative analysis of human chromosome 7q21 and mouse proximal chromosome 6 reveals a placental-specific imprinted gene, TFPI2/Tfpi2, which requires EHMT2 and EED for allelic-silencing. Genome Res 18(8):1270-81. [PubMed: 18480470]  [MGI Ref ID J:139777]

Niles KM; Chan D; La Salle S; Oakes CC; Trasler JM. 2011. Critical period of nonpromoter DNA methylation acquisition during prenatal male germ cell development. PLoS One 6(9):e24156. [PubMed: 21949694]  [MGI Ref ID J:177876]

Schulz R; McCole RB; Woodfine K; Wood AJ; Chahal M; Monk D; Moore GE; Oakey RJ. 2009. Transcript- and tissue-specific imprinting of a tumour suppressor gene. Hum Mol Genet 18(1):118-27. [PubMed: 18836209]  [MGI Ref ID J:143298]

Wood AJ; Bourc'his D; Bestor TH; Oakey RJ. 2007. Allele-specific demethylation at an imprinted mammalian promoter. Nucleic Acids Res 35(20):7031-9. [PubMed: 17942418]  [MGI Ref ID J:172174]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2450.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3185.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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