Strain Name:

B6(Cg)-Hdac3tm1.1Laz/J

Stock Number:

024119

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Availability:

Cryopreserved - Ready for recovery

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Hdac3flox/flox mice may be useful for studying HDAC3-induced gene silencing.

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.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   18-DEC-13
Specieslaboratory mouse
 
Donating Investigator Mitchell A Lazar,   UPENN

Description
These Hdac3flox/flox mutant mice possess loxP sites flanking exons 4-7 of the histone deacetylase 3 (Hdac3) gene. HDAC3 is an enzyme that regulates the acetylation of histone tails by modulating histone-DNA interactions resulting in gene silencing. HDAC3-induced silencing is involved in cell growth, apoptosis, neuronal plasticity, tumor suppression, transcriptional regulation, cell cycle progression, and development. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 4-7 deleted in the cre-expressing tissues.

For example, 2 weeks after infusion of adenoviral Cre recombinase in area CA1 of the dorsal hippocampus, HDAC3 deficiency results in enhanced long term memory.

When bred to B6.Cg-Tg(Fabp4-cre)1Rev/J mice (Stock No. 005069) expressing Cre recombinase in brown and white gonadal and subcutaneous adipose tissue, 50% of offspring died by postnatal day 5; no mice survived to adulthood.

When bred to B6;FVB-Tg(Adipoq-cre)1Evdr/J mice (Stock No. 010803) expressing Cre recombinase in adipose tissue, offspring lived to at least 6 months.

Development
A targeting vector was designed to insert a loxP site upstream of exon 4, and a frt-flanked neomycin resistance (neo) cassette followed by a second loxP site downstream of exon 7 of the histone deacetylase 3 (Hdac3) gene. The construct was electroporated into C57BL/6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred to C57BL/6J females. Offspring were bred with ACT-Flpe transgenic mice on a C57BL/6 background to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Hdac3tm1.1Laz/Hdac3tm1.1Laz

        C57BL/6-Hdac3tm1.1Laz   (conditional)
  • behavior/neurological phenotype
  • abnormal long term object recognition memory
    • 2 weeks after bilateral intrahippocampal infusion of adenoviral cre mice display enhanced long term memory for object location, forming memories following a 3 min training period that persist for up to 7 days   (MGI Ref ID J:168224)
    • however, no difference is detected in novel object recognition   (MGI Ref ID J:168224)
    • treatment with an siRNA for Nr4a2 blocks enhanced memory formation in adenoviral cre treated mice   (MGI Ref ID J:168224)

Hdac3tm1.1Laz/Hdac3tm1.1Laz

        involves: C57BL/6   (conditional)
  • liver/biliary system phenotype
  • hepatic steatosis
    • hepatosteatosis without obvious inflammation in mice injected with adenovirus expressing cre in the liver   (MGI Ref ID J:206152)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Hdac3tm1.1Laz/Hdac3tm1.1Laz Tg(Adipoq-cre)1Evdr/0

        involves: C57BL/6 * FVB   (conditional)
  • mortality/aging
  • *normal* mortality/aging
    • mice show no reduction in survival to at least 6 months   (MGI Ref ID J:199860)

Hdac3tm1.1Laz/Hdac3tm1.1Laz Tg(Fabp4-cre)1Rev/0

        involves: C57BL/6   (conditional)
  • mortality/aging
  • partial postnatal lethality
    • more than 50% die before postnatal day 5 (P5); remaining animals display failure to thrive and a wasting phenotype   (MGI Ref ID J:199860)
  • premature death
    • no viable adults are obtained; mice are born at the expected Mendelian ratio, but none survive beyond 25 days of age   (MGI Ref ID J:199860)
  • growth/size/body phenotype
  • cachexia
    • animals surviving past P5 fail to thrive and display a wasting phenotype   (MGI Ref ID J:199860)
View Research Applications

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

Cell Biology Research
Cell Cycle Regulation
Genes Regulating Growth and Proliferation
Transcriptional Regulation

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Hdac3tm1.1Laz
Allele Name targeted mutation 1.1, Mitchell A Lazar
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) HDAC3f; HDAC3flox;
Strain of OriginC57BL/6
Gene Symbol and Name Hdac3, histone deacetylase 3
Chromosome 18
Gene Common Name(s) AW537363; HD3; RPD3; RPD3-2; expressed sequence AW537363;
Molecular Note A loxP site was isnerted upstream of exon 4. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 7. Flp-mediated recombination removed the neo cassette and left exons 4 through 7 floxed. [MGI Ref ID J:178911]

Genotyping

Genotyping Information

Genotyping Protocols

Hdac3tm1.1Laz, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

McQuown SC; Barrett RM; Matheos DP; Post RJ; Rogge GA; Alenghat T; Mullican SE; Jones S; Rusche JR; Lazar MA; Wood MA. 2011. HDAC3 is a critical negative regulator of long-term memory formation. J Neurosci 31(2):764-74. [PubMed: 21228185]  [MGI Ref ID J:168224]

Additional References

Hdac3tm1.1Laz related

Alenghat T; Osborne LC; Saenz SA; Kobuley D; Ziegler CG; Mullican SE; Choi I; Grunberg S; Sinha R; Wynosky-Dolfi M; Snyder A; Giacomin PR; Joyce KL; Hoang TB; Bewtra M; Brodsky IE; Sonnenberg GF; Bushman FD; Won KJ; Lazar MA; Artis D. 2013. Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis. Nature 504(7478):153-7. [PubMed: 24185009]  [MGI Ref ID J:207697]

Feng D; Liu T; Sun Z; Bugge A; Mullican SE; Alenghat T; Liu XS; Lazar MA. 2011. A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism. Science 331(6022):1315-9. [PubMed: 21393543]  [MGI Ref ID J:169669]

Lewandowski SL; Janardhan HP; Smee KM; Bachman M; Sun Z; Lazar MA; Trivedi CM. 2014. Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis. Hum Mol Genet 23(14):3801-9. [PubMed: 24565863]  [MGI Ref ID J:210667]

Mullican SE; Gaddis CA; Alenghat T; Nair MG; Giacomin PR; Everett LJ; Feng D; Steger DJ; Schug J; Artis D; Lazar MA. 2011. Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. Genes Dev 25(23):2480-8. [PubMed: 22156208]  [MGI Ref ID J:178911]

Mullican SE; Tomaru T; Gaddis CA; Peed LC; Sundaram A; Lazar MA. 2013. A novel adipose-specific gene deletion model demonstrates potential pitfalls of existing methods. Mol Endocrinol 27(1):127-34. [PubMed: 23192980]  [MGI Ref ID J:199860]

Rogge GA; Singh H; Dang R; Wood MA. 2013. HDAC3 is a negative regulator of cocaine-context-associated memory formation. J Neurosci 33(15):6623-32. [PubMed: 23575859]  [MGI Ref ID J:196668]

Singh N; Gupta M; Trivedi CM; Singh MK; Li L; Epstein JA. 2013. Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression. Dev Biol 377(2):333-44. [PubMed: 23506836]  [MGI Ref ID J:196596]

Singh N; Trivedi CM; Lu M; Mullican SE; Lazar MA; Epstein JA. 2011. Histone deacetylase 3 regulates smooth muscle differentiation in neural crest cells and development of the cardiac outflow tract. Circ Res 109(11):1240-9. [PubMed: 21959220]  [MGI Ref ID J:196561]

Sun Z; Feng D; Fang B; Mullican SE; You SH; Lim HW; Everett LJ; Nabel CS; Li Y; Selvakumaran V; Won KJ; Lazar MA. 2013. Deacetylase-independent function of HDAC3 in transcription and metabolism requires nuclear receptor corepressor. Mol Cell 52(6):769-82. [PubMed: 24268577]  [MGI Ref ID J:206152]

Sun Z; Miller RA; Patel RT; Chen J; Dhir R; Wang H; Zhang D; Graham MJ; Unterman TG; Shulman GI; Sztalryd C; Bennett MJ; Ahima RS; Birnbaum MJ; Lazar MA. 2012. Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration. Nat Med 18(6):934-42. [PubMed: 22561686]  [MGI Ref ID J:187466]

Sun Z; Singh N; Mullican SE; Everett LJ; Li L; Yuan L; Liu X; Epstein JA; Lazar MA. 2011. Diet-induced Lethality Due to Deletion of the Hdac3 Gene in Heart and Skeletal Muscle. J Biol Chem 286(38):33301-9. [PubMed: 21808063]  [MGI Ref ID J:176726]

Yan Q; Carmody RJ; Qu Z; Ruan Q; Jager J; Mullican SE; Lazar MA; Chen YH. 2012. Nuclear factor-kappaB binding motifs specify Toll-like receptor-induced gene repression through an inducible repressosome. Proc Natl Acad Sci U S A 109(35):14140-5. [PubMed: 22891325]  [MGI Ref ID J:188579]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   18-DEC-13

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* $2140.00
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 10 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* $2782.00
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 10 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
   000664 C57BL/6J (approximate)
 
  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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