Description

Strain Information

Former Names STOCK Bdnftm2Jae/J    (Changed: 15-DEC-04 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N?F?+F13 (06-DEC-07)   Donating Investigator Rudolf Jaenisch,   Massachusetts Institute of Technology

Description
These mice possess loxP sites on either side of exon 5 of the targeted gene. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

When bred to a strain expressing Cre recombinase under the control of a tetracycline-responsive promoter element (see Stock No. 006224, 006234, 006244) and a strain expressing a tetracycline-controlled activator protein in brain tissues (see Stock No. 003763), this mutant mouse strain may be useful in studies of hippocampal-dependent learning and long-term potentiation.

When bred to a strain expressing Cre recombinase in neuronal cells (see Stock No. 003966 for example), this mutant mouse strain may be useful in studies of epilepsy.

Development
A loxP site flanked targeting vector containing hygromycin resistance and thymidine kinase genes under the control of the cytomegalovirus promoter was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 5 of the targeted gene, and another loxP site was inserted upstream of exon 5. This construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells which were transiently transfected with a Cre-recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into BALB/c blastocysts.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Bdnf

002266	B6.129S4-Bdnftm1Jae/J
002267	STOCK Bdnftm1Jae/J

View Strains carrying other alleles of Bdnf     (2 strains)

Additional Web Information

Cre-lox Systems

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.

Bdnf^tm3Jae/Bdnf^tm3Jae

        involves: 129S4/SvJae

• normal phenotype
• no abnormal phenotype detected (MGI Ref ID J:71969)

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

Bdnf^tm3Jae/Bdnf^tm3Jae Tg(Eno2tTA)5030Nes/0 Tg(tetO-cre)1Jaw/0

        involves: 129/Sv * C57BL/6 * ICR * SJL   (conditional)

• behavior/neurological phenotype
• abnormal contextual conditioning (MGI Ref ID J:91563)
  • contextual learning is impaired in mutants when doxycycline treatment is stopped at 3 months of age compared to mutant littermates maintained on doxycycline
  • contextual learning is virtually absent in mutants when no doxycycline treatment is given throughout development
• abnormal cued conditioning behavior (MGI Ref ID J:91563)
  • cued learning is normal in mutants when doxycycline treatment is stopped at 3 months of age but impaired when no doxycycline treatment is given throughout development
• hyperactivity (MGI Ref ID J:91563)
  • mutants bred without doxycycline treatment are hyperactive compared to mutants bred with doxycycline treatment
  • hyperactivity is not seen when doxycycline treatment is stopped at 3 months of a
• homeostasis/metabolism phenotype
• decreased sensitivity to xenobiotics (MGI Ref ID J:91563)
  • no response is seen to the antidepressant desipramine in mutants when doxycycline treatment is stopped at 3 months of age
• nervous system phenotype
• reduced long term potentiation (MGI Ref ID J:91563)
  • long term potentiation is impaired requiring a greater amplitude stimulus to evoke any response in mutants when doxycycline treatment is stopped at 3 months of age compared to mutant littermates maintained on doxycycline

Bdnf^tm3Jae/Bdnf^tm3Jae Tg(Syn1-cre)671Jxm/0

        involves: 129/Sv * C57BL/6 * ICR   (conditional)

• behavior/neurological phenotype
• kindling (MGI Ref ID J:91467)
  • an increased number of stimulations are required to initiate kindling behavior, however once initiated progression through subsequent classes of kindling is the same as in wild-type mice and no increase in the current required to induce the initial electrographic seizure is seen
• nervous system phenotype
• kindling (MGI Ref ID J:91467)
  • an increased number of stimulations are required to initiate kindling behavior, however once initiated progression through subsequent classes of kindling is the same as in wild-type mice and no increase in the current required to induce the initial electrographic seizure is seen

View Research Applications

Research Applications

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

Neurobiology Research
Cre-lox System (loxP-flanked Sequences)

Research Tools
Cre-lox System (loxP-flanked Sequences)
Diabetes and Obesity Research (loxP)

Bdnf^tm3Jae related

Apoptosis Research
Extracellular Modulators

Neurobiology Research
Neurotrophic Factor Defects
Vestibular and Hearing Defects

Sensorineural Research
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Bdnftm3Jae
Allele Name		targeted mutation 3, Rudolf Jaenisch
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Bdnf2L; Bdnf2lox;
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Bdnf, brain derived neurotrophic factor
Chromosome		2
Gene Common Name(s)		MGC105254; MGC34632;
Molecular Note		A single loxP site was inserted 5' to the only coding exon, and a loxP-flanked hygromycin resistance cassette was inserted 3' to the exon. The hygromycin selection cassette was removed in ES cells by transient Cre expression leaving a single loxP site prior to the production of chimeric mice. [MGI Ref ID J:71969]

Genotyping

Genotyping Information

Genotyping Protocols

Bdnf^tm3Jae, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Rios M; Fan G; Fekete C; Kelly J; Bates B; Kuehn R; Lechan RM; Jaenisch R. 2001. Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol 15(10):1748-57. [PubMed: 11579207]  [MGI Ref ID J:71969]

Additional References

Okayasu I; Yamada Y; Maeda T; Yoshida N; Koga Y; Oi K. 2004. The involvement of brain-derived neurotrophic factor in the pattern generator of mastication. Brain Res 1016(1):40-7. [PubMed: 15234250]  [MGI Ref ID J:91229]

Bdnf^tm3Jae related

Akbarian S; Rios M; Liu RJ; Gold SJ; Fong HF; Zeiler S; Coppola V; Tessarollo L; Jones KR; Nestler EJ; Aghajanian GK; Jaenisch R. 2002. Brain-derived neurotrophic factor is essential for opiate-induced plasticity of noradrenergic neurons. J Neurosci 22(10):4153-62. [PubMed: 12019333]  [MGI Ref ID J:76683]

Berton O; McClung CA; Dileone RJ; Krishnan V; Renthal W; Russo SJ; Graham D; Tsankova NM; Bolanos CA; Rios M; Monteggia LM; Self DW; Nestler EJ. 2006. Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311(5762):864-8. [PubMed: 16469931]  [MGI Ref ID J:105490]

Chan JP; Unger TJ; Byrnes J; Rios M. 2006. Examination of behavioral deficits triggered by targeting Bdnf in fetal or postnatal brains of mice. Neuroscience 142(1):49-58. [PubMed: 16844311]  [MGI Ref ID J:113166]

Chang Q; Khare G; Dani V; Nelson S; Jaenisch R. 2006. The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression. Neuron 49(3):341-8. [PubMed: 16446138]  [MGI Ref ID J:106973]

Graham DL; Edwards S; Bachtell RK; Dileone RJ; Rios M; Self DW. 2007. Dynamic BDNF activity in nucleus accumbens with cocaine use increases self-administration and relapse. Nat Neurosci 10(8):1029-37. [PubMed: 17618281]  [MGI Ref ID J:124163]

Hashimoto T; Bergen SE; Nguyen QL; Xu B; Monteggia LM; Pierri JN; Sun Z; Sampson AR; Lewis DA. 2005. Relationship of brain-derived neurotrophic factor and its receptor TrkB to altered inhibitory prefrontal circuitry in schizophrenia. J Neurosci 25(2):372-83. [PubMed: 15647480]  [MGI Ref ID J:97675]

He XP; Kotloski R; Nef S; Luikart BW; Parada LF; McNamara JO. 2004. Conditional deletion of TrkB but not BDNF prevents epileptogenesis in the kindling model. Neuron 43(1):31-42. [PubMed: 15233915]  [MGI Ref ID J:91467]

Heldt SA; Stanek L; Chhatwal JP; Ressler KJ. 2007. Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Mol Psychiatry 12(7):656-70. [PubMed: 17264839]  [MGI Ref ID J:137002]

Hill JJ; Kolluri N; Hashimoto T; Wu Q; Sampson AR; Monteggia LM; Lewis DA. 2005. Analysis of pyramidal neuron morphology in an inducible knockout of brain-derived neurotrophic factor. Biol Psychiatry 57(8):932-4. [PubMed: 15820715]  [MGI Ref ID J:102119]

Huang YZ; Pan E; Xiong ZQ; McNamara JO. 2008. Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse. Neuron 57(4):546-58. [PubMed: 18304484]  [MGI Ref ID J:135687]

Lyckman AW; Fan G; Rios M; Jaenisch R; Sur M. 2005. Normal eye-specific patterning of retinal inputs to murine subcortical visual nuclei in the absence of brain-derived neurotrophic factor. Vis Neurosci 22(1):27-36. [PubMed: 15842738]  [MGI Ref ID J:105280]

Monteggia LM; Barrot M; Powell CM; Berton O; Galanis V; Gemelli T; Meuth S; Nagy A; Greene RW; Nestler EJ. 2004. Essential role of brain-derived neurotrophic factor in adult hippocampal function. Proc Natl Acad Sci U S A 101(29):10827-32. [PubMed: 15249684]  [MGI Ref ID J:91563]

Zhao J; Seereeram A; Nassar MA; Levato A; Pezet S; Hathaway G; Morenilla-Palao C; Stirling C; Fitzgerald M; McMahon SB; Rios M; Wood JN. 2006. Nociceptor-derived brain-derived neurotrophic factor regulates acute and inflammatory but not neuropathic pain. Mol Cell Neurosci 31(3):539-48. [PubMed: 16413788]  [MGI Ref ID J:106864]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain originated on a mixed C;129S4 background. The Donating Investigator maintained it as as a homozygote on a mixed B6, 129S4, BALB/c background. Coat color expected from breeding:Albino
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	None Available
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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Contact Information
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Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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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