Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Timothy 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

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Dnmt3l^tm1Bes/Dnmt3l^tm1Bes

        involves: 129S6/SvEvTac

• lethality-prenatal/perinatal
• prenatal lethality (MGI Ref ID J:73452)
  • no viable embryos are recovered at birth from homozygous females
• cardiovascular system phenotype
• pericardial edema (MGI Ref ID J:73452)
  • pericardial edema is seen in embryos from homozygous females
• embryogenesis phenotype
• abnormal chorioallantoic fusion (MGI Ref ID J:73452)
  • the chorio-allantoic fusion fails in embryos from homozygous females
• abnormal chorion morphology (MGI Ref ID J:73452)
• abnormal ectoplacental cone (MGI Ref ID J:73452)
  • excess maternal blood is found near the ectoplacental cone in embryos from homozygous females
• abnormal trophoblast layer morphology (MGI Ref ID J:73452)
  • the secondary trophoblastic giant cells hyperproliferate resulting in overgrowth of the chorion that is seen in embryos from homozygous females
• abnormal trophoblast giant cells (MGI Ref ID J:73452)
  • the secondary trophoblastic giant cells hyperproliferate
• abnormal yolk sac morphology (MGI Ref ID J:73452)
  • hyperproliferation of the yolk sac endoderm is seen in embryos from homozygous females
• endocrine/exocrine gland phenotype
• small testis (MGI Ref ID J:73452)
  • adult males have severe hypogonadism
• homeostasis/metabolism phenotype
• pericardial edema (MGI Ref ID J:73452)
  • pericardial edema is seen in embryos from homozygous females
• reproductive system phenotype
• abnormal oogenesis (MGI Ref ID J:73452)
  • failure of maternal methylated gene imprinting is seen in homozygous females
• abnormal spermatogenesis (MGI Ref ID J:128710)
  • 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
  • male germ cells exhibit abnormal methylation of paternally imprinted genes
• azoospermia (MGI Ref ID J:73452)
  • seminiferous tubules contain only Sertoli cells
• decreased male germ cell number (MGI Ref ID J:128710)
  • by P10, males have about a quarter of the number of germ cells as heterozygous littermates
• azoospermia (MGI Ref ID J:73452)
  • seminiferous tubules contain only Sertoli cells
• infertility (MGI Ref ID J:73452)
  • both sexes are sterile
• small testis (MGI Ref ID J:73452)
  • adult males have severe hypogonadism
• nervous system phenotype
• exencephaly (MGI Ref ID J:73452)
  • exencephaly and other neural tube defects are seen in embryos from homozygous females

View Research Applications

Research Applications

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

Dnmt3l^tm1Bes 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

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 Origin		129S6/SvEvTac
ES Cell Line Name		CSL3
ES Cell Line Strain		129S6/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; MGC1090; 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

NEOTD (Generic Neo), STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

Dnmt3l^tm1Bes 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]

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]

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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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