Description

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 System Heterozygote x Heterozygote         (Female x Male)   02-APR-13 Species laboratory mouse Generation N10pN1+ (29-APR-13) Generation Definitions   Donating Investigator Kevin R. Jones,   University of Colorado- Boulder

Description
Brain derived neurotrophic factor is important for survival of neurons, regulates neuronal differentiation and is involved in synaptic plasticity as well as mediation of food intake and body weight. These mice possess loxP sites on either side of exon 5 of the targeted gene, with polyadenylation sequence upstream of the 3' loxP site, and lacZ downstream of the 3' loxP site. Mice that are homozygous for this allele are viable, obese and are poor breeders. The Donating Investigator reports that homozygotes exhibit subtle neurological abnormalities. The phenotype of homozygotes is probably due to disruption by insertion of lacZ and loxP sites into the locus. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 5 deleted and express lacZ in the cre-expressing tissues.

When bred to mice carrying Tg(Wnt1-cre)11Rth (see Stock No. 009107 for example) Cre recombinase expression in midbrain/neural tube results in exhibit hindlimb clutching, poor rotarod performance, and alterations in the substantia nigra.

Development
A targeting vector designed by Dr. Kevin R. Jones (University of Colorado, Boulder) was used to flank exon 5 with loxP sites and insert a polyadenylation sequence upstream of the 3' loxP site, and lacZ and a FRT site flanked PGK-NEO cassette downstream of the 3' loxP site. This construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice. The mice were then crossed to a FLP recombinase expressing strain on an unspecified genetic background (and containing B6 and SJL) to remove the FRT site flanked PGK-NEO cassette. The mice were then backcrossed to C57BL/6 for more than 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Bdnf

002266	B6.129S4-Bdnftm1Jae/J
002267	STOCK Bdnftm1Jae/J
004339	STOCK Bdnftm3Jae/J

View Strains carrying other alleles of Bdnf     (3 strains)

Additional Web Information

Use of MICE by companies or for-profit entities requires a license prior to shipping.
Use of MICE by companies or for-profit entities requires a license.

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. Bulimia Nervosa, Susceptibility to, 1; BULN1   (BDNF) Central Hypoventilation Syndrome, Congenital; CCHS   (BDNF) Obsessive-Compulsive Disorder; OCD   (BDNF)

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.

Bdnf^tm1Krj/Bdnf^tm1Krj

        involves: 129S2/SvPas * C57BL/6

• nervous system phenotype
• *normal* nervous system phenotype
  • dendritic arborization of layer 2/3 pyramidal neurons in the visual cortex is normal at 3 weeks and at 4 months   (MGI Ref ID J:184139)
  • basal response properties of the visual cortex are normal   (MGI Ref ID J:184139)
• • abnormal GABAergic neuron morphology
    • GABAergic innervation of the visual cortex is deficient   (MGI Ref ID J:184139)
  • abnormal dendrite morphology
    • distal segment density of both basal and apical dendrites is elevated at 4 months of age   (MGI Ref ID J:184139)
    • spine length and head diameter are not altered at 4 months as they are in controls   (MGI Ref ID J:184139)
  • abnormal nervous system physiology
    • recovery from monocular deprivation in the visual cortex fails to occur as expected   (MGI Ref ID J:184139)
    • maintenance of cortical responsiveness is impaired   (MGI Ref ID J:184139)
  • • abnormal nervous system electrophysiology
      • spontaneous firing rate deviates from controls   (MGI Ref ID J:184139)

Bdnf^tm1Krj/Bdnf^tm1Lfr Tg(Wnt1-cre)11Rth/0

        involves: 129S2/SvPas * C57BL/6 * CBA   (conditional)

• behavior/neurological phenotype
• impaired coordination
  • at 4 - 5 weeks of age performance on the rotarod test is impaired   (MGI Ref ID J:99291)
• limb grasping
  • at 1 month of age 78% of mutants clutch compared to 8% of wild-type mice and by 6 months all mutants clutch compared to 16% of wild-type   (MGI Ref ID J:99291)
• nervous system phenotype
• abnormal substantia nigra morphology
  • tyrosine hydroxylase-positive neurons are reduced by about 27% and 23% at postnatal day 0 and 120, respectively and appear disorganized   (MGI Ref ID J:99291)
  • the extent of the substantia nigra pars compacta appears reduced in coronal sections but the density of calbindin-positive neurons appears increased   (MGI Ref ID J:99291)

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

Bdnf^tm1Krj/Bdnf⁺ Emx1^tm1(cre)Krj/Emx1⁺

        involves: 129S2/SvPas * C57BL/6J   (conditional)

• growth/size phenotype
• *normal* growth/size phenotype
  • forebrain specific heterozygotes do not become obese unlike mice heterozygous for Bdnf^tm1Lfr   (MGI Ref ID J:84683)

View Research Applications

Research Applications

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

Neurobiology Research
lacZ expression in neural tissue
Cre-lox System
      loxP-flanked Sequences

Research Tools
lacZ Expression
Cre-lox System
      loxP-flanked Sequences: Test/Reporter
Diabetes and Obesity Research
      lacZ

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Bdnftm1Krj
Allele Name		targeted mutation 1, Kevin R Jones
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		BDNFlox; Bdnfklox;
Strain of Origin		129S2/SvPas
Gene Symbol and Name		Bdnf, brain derived neurotrophic factor
Chromosome		2
Gene Common Name(s)		ANON2; BULN2;
Molecular Note		A targeting construct was designed to flank the pro encoding region and mature hormone-encoding region of exon V with loxP sites, with a trimerized polyadenylation signal just upstream of the 3' loxP sequence and a lacZ gene just downstream of the 3' loxP sequence. Cre mediated excision would enable transcription and translation of lacZ in place of Bdnf. [MGI Ref ID J:84683]

Genotyping

Genotyping Information

Genotyping Protocols

Bdnf^tm1Krj, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Gorski JA; Zeiler SR; Tamowski S; Jones KR. 2003. Brain-derived neurotrophic factor is required for the maintenance of cortical dendrites. J Neurosci 23(17):6856-65. [PubMed: 12890780]  [MGI Ref ID J:84683]

Additional References

Bdnf^tm1Krj related

An JJ; Gharami K; Liao GY; Woo NH; Lau AG; Vanevski F; Torre ER; Jones KR; Feng Y; Lu B; Xu B. 2008. Distinct role of long 3' UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons. Cell 134(1):175-87. [PubMed: 18614020]  [MGI Ref ID J:138312]

Baquet ZC; Bickford PC; Jones KR. 2005. Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci 25(26):6251-9. [PubMed: 15987955]  [MGI Ref ID J:99291]

Baquet ZC; Gorski JA; Jones KR. 2004. Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brain-derived neurotrophic factor. J Neurosci 24(17):4250-8. [PubMed: 15115821]  [MGI Ref ID J:96903]

Baydyuk M; Russell T; Liao GY; Zang K; An JJ; Reichardt LF; Xu B. 2011. TrkB receptor controls striatal formation by regulating the number of newborn striatal neurons. Proc Natl Acad Sci U S A 108(4):1669-74. [PubMed: 21205893]  [MGI Ref ID J:168326]

Baydyuk M; Xie Y; Tessarollo L; Xu B. 2013. Midbrain-derived neurotrophins support survival of immature striatal projection neurons. J Neurosci 33(8):3363-9. [PubMed: 23426664]  [MGI Ref ID J:194255]

English CN; Vigers AJ; Jones KR. 2012. Genetic evidence that brain-derived neurotrophic factor mediates competitive interactions between individual cortical neurons. Proc Natl Acad Sci U S A 109(47):19456-61. [PubMed: 23129644]  [MGI Ref ID J:192261]

Fox EA; Biddinger JE; Jones KR; McAdams J; Worman A. 2013. Mechanism of hyperphagia contributing to obesity in brain-derived neurotrophic factor knockout mice. Neuroscience 229:176-99. [PubMed: 23069761]  [MGI Ref ID J:193539]

Gorski JA; Balogh SA; Wehner JM; Jones KR. 2003. Learning deficits in forebrain-restricted brain-derived neurotrophic factor mutant mice. Neuroscience 121(2):341-54. [PubMed: 14521993]  [MGI Ref ID J:100000]

Kaneko M; Xie Y; An JJ; Stryker MP; Xu B. 2012. Dendritic BDNF synthesis is required for late-phase spine maturation and recovery of cortical responses following sensory deprivation. J Neurosci 32(14):4790-802. [PubMed: 22492034]  [MGI Ref ID J:184139]

Rocha-Sanchez SM; Morris KA; Kachar B; Nichols D; Fritzsch B; Beisel KW. 2007. Developmental expression of Kcnq4 in vestibular neurons and neurosensory epithelia. Brain Res 1139:117-25. [PubMed: 17292869]  [MGI Ref ID J:118633]

Strand AD; Baquet ZC; Aragaki AK; Holmans P; Yang L; Cleren C; Beal MF; Jones L; Kooperberg C; Olson JM; Jones KR. 2007. Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration. J Neurosci 27(43):11758-68. [PubMed: 17959817]  [MGI Ref ID J:127037]

Vigers AJ; Amin DS; Talley-Farnham T; Gorski JA; Xu B; Jones KR. 2012. Sustained expression of brain-derived neurotrophic factor is required for maintenance of dendritic spines and normal behavior. Neuroscience 212:1-18. [PubMed: 22542678]  [MGI Ref ID J:184800]

Waterhouse EG; An JJ; Orefice LL; Baydyuk M; Liao GY; Zheng K; Lu B; Xu B. 2012. BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission. J Neurosci 32(41):14318-30. [PubMed: 23055503]  [MGI Ref ID J:190905]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes are viable, but are obese and breed poorly.
Mating System	Heterozygote x Heterozygote         (Female x Male)   02-APR-13
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

 

This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 17-JUN-13

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

Control Information

	Control
	000664 C57BL/6J
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.

See Terms of Use tab for General Terms and Conditions

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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