JAX Mouse Strain Datasheet - 006579

C57BL/6-Tg(Camk2a-Bdnf)A9Stl/J

Stock No:: 006579 |; BDNF

Cryo Recovery

Overview

Also Known As: BDNF

These BDNF mice express a transgene containing the rat brain-derived neurotrophic factor driven by the Camk2a promoter affecting maturation and plasticity of the visual cortex.

Donating Investigator

Dr. Susumu Tonegawa, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation

Tg(Camk2a-Bdnf)A9Stl

Allele Type
Transgenic (Inserted expressed sequence)

View Genetics

Research Applications

Neurobiology Research
Research Tools
Sensorineural Research

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

Hemizygous mice are viable and fertile, although the donating investigator reports that hemizygous mice have breeding problems likely resulting from a social anxiety-related phenotype. These "BDNF (line A9)" mice express the rat brain-derived neurotrophic factor (BDNF) primarily in forebrain regions, including the neocortex and hippocampus. Weak transgenic BDNF expression is detected also in cerebellum. Within the primary visual cortex, transgene expression is highest in the superficial layers. Hemizygous mice exhibit accelerated maturation of GABAergic innervation and inhibition, earlier termination of the critical period for ocular dominance plasticity, and accelerated development of visual acuity. These transgenic mice may be useful for studies involving BDNF overexpression and synaptic maturation and plasticity in the visual cortex.

Development

A rat Bdnf cDNA sequence (modified with a Kozac sequence inserted in front of the translation initiation codon) and a SV40 intron and polyadenylation sequence was placed downstream of the 8.5 kb promoter region from mouse Camk2a. This transgene was injected into the pronuclei of C57BL/6 embryos. The donating investigator reported that the resulting chimeric founders (line A9) were subsequently bred to C57BL/6 mice (see SNP note below) and maintained on that genetic background for many generations prior to arrival at The Jackson Laboratory.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Expression Data

Expressed Gene	Bdnf, brain-derived neurotrophic factor, rat
Site of Expression

Control Suggestions

Noncarrier
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Huang ZJ; Kirkwood A; Pizzorusso T; Porciatti V; Morales B; Bear MF; Maffei L; Tonegawa S. 1999. BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell 98(6):739-55. PubMed: 10499792 MGI: J:57645

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Genetics

Tg(Camk2a-Bdnf)A9Stl

Allele Symbol: Tg(Camk2a-Bdnf)A9Stl

Allele Name	transgene insertion A9, Susumu Tonegawa
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)
Gene Symbol and Name	Tg(Camk2a-Bdnf)A9Stl, transgene insertion A9, Susumu Tonegawa
Gene Synonym(s)
Promoter	Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory
Expressed Gene	Bdnf, brain-derived neurotrophic factor, rat
Strain of Origin	(C57BL/6 x DBA/2)F2
Chromosome	UN
Molecular Note	The transgene construct has the rat Bdnf cDNA sequence, with a Kozak sequence inserted in front of the translation initiation site, controlled by the mouse Camk2a promoter. The SV40 intron/polyA sequence was inserted the 3' to the Bdnf cDNA. ISH demonstrated that Bdnf overexpression is mainly restricted to the forebrain regions, including all of the neocortex, parts of the hippocampus, amygdala and striatum.
Mutations Made By	Dr. Susumu Tonegawa, Massachusetts Institute of Technology

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Cortical Defects
Research Tools
- Neurobiology Research
- Sensorineural Research
Sensorineural Research
- Eye Defects

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Camk2a-Bdnf)A9Stl/0
C57BL/6-Tg(Camk2a-Bdnf)A9Stl/J

behavior/neurological phenotype

abnormal behavior
- however, mice show normal behavior in the social approach test and in the forced swim test
- mice bury less marbles than wild-type mice

decreased anxiety-related response
- mice spend more time in the open arms of the elevated plus-maze and make more entries to the open arms than wild-type mice

psychomotor seizures
- seizures are similar to stage 5 limbic seizures

seizures
- mice exhibit spontaneous seizures after 5 months of age, with 3 of 12 mice showing seizures at 9 months of age
- seizure behavior includes head bobbing, forelimb and hindlimb clonus that progresses into running and jumping seizures followed by falling and the continuation of head bobbing and forelimb clonus

growth/size/body region phenotype

decreased body weight
- mice show decreased body weight that becomes more pronounced with age

nervous system phenotype

psychomotor seizures
- seizures are similar to stage 5 limbic seizures

seizures
- mice exhibit spontaneous seizures after 5 months of age, with 3 of 12 mice showing seizures at 9 months of age
- seizure behavior includes head bobbing, forelimb and hindlimb clonus that progresses into running and jumping seizures followed by falling and the continuation of head bobbing and forelimb clonus

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

Genotype: Tg(Camk2a-Bdnf)A9Stl/0
involves: C57BL/6 * DBA/2

nervous system phenotype

abnormal brain interneuron morphology
- at P17, number of Parvalbumin-positive interneurons in the visual cortex is ~double the number found in wild-type brains
- these interneurons have larger soma sizes and more extensive neurite arborizations than in wild-type at P17

abnormal inhibitory postsynaptic currents
- EPSC amplitudes and whole-cell capacitances are similar between transgenic and wild-type mice
- in layer III pyramidal neurons in hippoccampal slices, amplitude of the maximal IPSC (462 pA) is consistently large than in wild-type (279 pA)
- stimulus intensity required to recruit a saturating IPSC is similar in wild-type and transgenic brain slices

abnormal neocortex morphology
- at 5 weeks, BDNF mRNA levels in neocortex of transgenic mice are ~3-fold higher than in wild-type littermates

abnormal neuron differentiation
- development of GABAergic neurons is accelerated in the primary visual cortex of transgenic mice between P12 and P35, relative to wild-type mice

abnormal visual cortex morphology
- ocular dominance (OD) plasticity ends prematurely in transgenic mice relative to wild-type; the OD shift induced by 4-day monocular deprivation (MD) is blocked when done at P28, near the peak of OD shift in wild-type
- shifts in the contralateral/ipsilateral visual-evoked potential (C/I VEP) ratios are larger in transgenics when MD is done with a difference of ~1 week compared to wild-type

nervous system phenotype
- brain development at 4 weeks is grossly normal; cortex is of normal thickness, and lamination is intact with normal neuronal cell density in the visual cortex

reduced long term potentiation
- WM->III LTP undergoes a sharp decline between 3 and 4 weeks postnatal, which is 1 week earlier than observed in wild-type littermates (between 4 and 5 weeks of age)
- theta burst stimulation (TBS) at the white matter-layer IV border (WM->III) induces little LTP in transgenic mice (101%), compared to the robust LTP induced in wild-type mice (122%)
- when inhibition is induced in cortical slices from transgenic mice with picrotoxin application, WM->III LTP can be supported by mice at P23-P25

vision/eye phenotype

abnormal eye physiology
- visual acuity is accelerated in transgenic mice relative to wild-type; visual acuity reaches adult levels by P24-25, a week sooner than in wild-type

cellular phenotype

abnormal neuron differentiation
- development of GABAergic neurons is accelerated in the primary visual cortex of transgenic mice between P12 and P35, relative to wild-type mice

References

Huang ZJ; Kirkwood A; Pizzorusso T; Porciatti V; Morales B; Bear MF; Maffei L; Tonegawa S. 1999. BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex. Cell 98(6):739-55. PubMed: 10499792 MGI: J:57645

Additional - Tg(Camk2a-Bdnf)A9Stl 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: J:138312
Cunha C; Angelucci A; D'Antoni A; Dobrossy MD; Dunnett SB; Berardi N; Brambilla R. 2009. Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments. Neurobiol Dis 33(3):358-68. PubMed: 19095063 MGI: J:146304
Gharami K; Xie Y; An JJ; Tonegawa S; Xu B. 2008. Brain-derived neurotrophic factor over-expression in the forebrain ameliorates Huntington's disease phenotypes in mice. J Neurochem 105(2):369-79. PubMed: 18086127 MGI: J:135260
Gianfranceschi L; Siciliano R; Walls J; Morales B; Kirkwood A; Huang ZJ; Tonegawa S; Maffei L. 2003. Visual cortex is rescued from the effects of dark rearing by overexpression of BDNF. Proc Natl Acad Sci U S A 100(21):12486-91. PubMed: 14514885 MGI: J:128269
Isgor C; Pare C; McDole B; Coombs P; Guthrie K. 2015. Expansion of the dentate mossy fiber-CA3 projection in the brain-derived neurotrophic factor-enriched mouse hippocampus. Neuroscience 288:10-23. PubMed: 25555929 MGI: J:221440
McDole B; Isgor C; Pare C; Guthrie K. 2015. BDNF over-expression increases olfactory bulb granule cell dendritic spine density in vivo. Neuroscience 304:146-60. PubMed: 26211445 MGI: J:226270
Wang BS; Feng L; Liu M; Liu X; Cang J. 2013. Environmental Enrichment Rescues Binocular Matching of Orientation Preference in Mice that Have a Precocious Critical Period. Neuron 80(1):198-209. PubMed: 24012279 MGI: J:201829
Weidner KL; Buenaventura DF; Chadman KK. 2014. Mice over-expressing BDNF in forebrain neurons develop an altered behavioral phenotype with age. Behav Brain Res 268:222-8. PubMed: 24768643 MGI: J:216846

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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.

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Also Known As: BDNF

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(Camk2a-Bdnf)A9Stl

Allele Symbol: Tg(Camk2a-Bdnf)A9Stl

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Camk2a-Bdnf)A9Stl/0C57BL/6-Tg(Camk2a-Bdnf)A9Stl/J

behavior/neurological phenotype

growth/size/body region phenotype

nervous system phenotype

Genotype: Tg(Camk2a-Bdnf)A9Stl/0involves: C57BL/6 * DBA/2

nervous system phenotype

vision/eye phenotype

cellular phenotype

References

Additional - Tg(Camk2a-Bdnf)A9Stl related

Genotyping Protocols

Breeding Considerations

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(Camk2a-Bdnf)A9Stl/0
C57BL/6-Tg(Camk2a-Bdnf)A9Stl/J

Genotype: Tg(Camk2a-Bdnf)A9Stl/0
involves: C57BL/6 * DBA/2