Overview

Also Known As:BDNF^-

These Bdnf knock-out mice exhibit severe deficiencies in coordination and balance, associated with excessive degeneration in several sensory ganglia including the vestibular ganglion.

Donating Investigator

Rudolf Jaenisch, Whitehead Institute, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation

Bdnf^tm1Jae

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Bdnf	brain derived neurotrophic factor

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Research Applications

Sensorineural Research
Apoptosis Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice heterozygous for the Bdnf^tm1Jae mutation show about 1/2 normal levels of Bdnf mRNA, but appear normal. Mice homozygous for the Bdnf^tm1Jae mutation are smaller than normal siblings and most die within the second postnatal week. They have defective coordination of movements and balance. They also exhibit head bobbing and spinning during periods of hyperactivity. There are rare survivors to adulthood. There is excessive degeneration in all sensory ganglia examined, including the vestibular ganglion. Motor neurons are not affected. BDNF can prevent death of central motor neurons and other neurons in vitro, but does not affect these in vivo.

Development

The Bdnf^tm1Jae mutant strain was developed in the laboratory of Dr. Rudolf Jaenisch at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology. A part of exon 5 of the gene was deleted and replaced by a neomycin cassette. This deletion left 49 and 30 amino acids in the N and C termini, respectively. The 129-derived J1 ES cell line was used.

Control Suggestions

This strain is a mixture of 129, BALB/c, and C57BL/6 inbred strains. Wildtype mice from the colony may be used as controls.
Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Ernfors P; Lee KF; Jaenisch R. 1994. Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature 368(6467):147-50PubMed: 8139657 MGI: J:17123

View All References

Genetics

Bdnf^tm1Jae

Allele Symbol: Bdnf^tm1Jae

Allele Name	targeted mutation 1, Rudolf Jaenisch
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	BDNF^-; BDNF-KO
Gene Symbol and Name	Bdnf, brain derived neurotrophic factor
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	2
Molecular Note	A part of exon 5 of the gene was deleted and replaced by a neomycin cassette. This deletion left 49 and 30 amino acids in the N and C termini, respectively. Northern blot analysis on RNA derived from cerebral cortex showed that no detectable transcript is expressed from this allele.
Mutations Made By	Rudolf Jaenisch, Whitehead Institute, Massachusetts Institute of Technology

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Sensorineural Research
- Nociception

Genotype: Bdnf^tm1Jae related

Apoptosis Research
- Extracellular Modulators
Neurobiology Research
- Neurotrophic Factor Defects
- Hearing Defects
Sensorineural Research
- Hearing Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Bdnf^tm1Jae/Bdnf^tm1Jae
involves: 129S4/SvJae

behavior/neurological phenotype

circling

spinning

impaired balance

head bobbing

head tilt

impaired limb coordination

hyperactivity

digestive/alimentary phenotype

abnormal fungiform papillae morphology
- loss of fungiform papillae is seen in 2 week old mutants and remaining papillae are smaller

growth/size/body region phenotype

abnormal fungiform papillae morphology
- loss of fungiform papillae is seen in 2 week old mutants and remaining papillae are smaller

decreased body size
- mice are reduced in size compared to control littermates

hearing/vestibular/ear phenotype

abnormal type I vestibular cell
- no nerve chalicies are found associated with type I hair cells of the vestibule

deafness
- loss of hearing

abnormal crista ampullaris morphology
- ampullar cristae completely lack innervation

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - innervation of the cochlear inner and outer hair cells appears similar to controls
- Normal - despite abnormal innervation of the vestibular compartment, the structural integrity of the organ of Corti, macula of the saccula and utricle, and the cristae of the semicircular ducts appear similar to controls
- Normal - mice respond to auditory stimuli

nervous system phenotype
- Normal - no differences are seen in the morphology of the central and peripheral nerve processes from the trigeminal, geniculate, petrose and nodose ganglia at E10.5-11.5

mortality/aging

postnatal lethality, incomplete penetrance
- most homozygotes die in the second postnatal week, with rare survivors achieving adult stages

nervous system phenotype

abnormal vestibular nerve morphology
- only small fiber bundles enter the saccule, utricle and ampulla of the semicircular ducts compared to controls; the remaining fibers terminate in the connective tissue adjacent to the sensory epithelia of the saccule, utricle and cristae of the semicurcular ducts
- ar ducts
- innervation of the vestibular compartment of the inner ear is severely compromised
- no nerve chalicies are found associated with type I hair cells of the vestibule

decreased sensory neuron number
- Normal - the number of facial motor neurons and sympathetic superior cervical ganglion neurons is not different from controls
- significant loss of all sensory neuron types in the nodose-petrosal, geniculate and vestibular ganglia in homozygous mice
- the numbers of neurons in many sensory ganglia are reduced compared to controls
- Normal - no difference in the number of facial motor neurons is seen compared to controls

small L4 dorsal root ganglion
- approximately 30% of the neurons are lost from the L4 DRG at P14-16

small petrosal ganglion
- greater than half of the neurons are lost from the nodose-petrosal ganglion at E18.5

small trigeminal ganglion
- approximately half of the neurons are lost from the trigeminal ganglion at P14-16

small geniculate ganglion
- approximately half of the neurons are lost from the geniculate ganglion at E18.5

small nodose ganglion
- approximately 65% of the neurons are lost from the nodose ganglion at P14-16
- greater than half of the neurons are lost from the nodose-petrosal ganglion at E18.5

abnormal innervation
- ampullar cristae completely lack innervation

abnormal sensory neuron innervation pattern
- loss of outer hair cell innervation in the apex, middle and basal turns of the cochlea

abnormal type I vestibular cell
- no nerve chalicies are found associated with type I hair cells of the vestibule

abnormal vestibular ganglion morphology
- in co-cultures of wild-type vestibular ganglion neurons with mutant hair cells, very few (2 of 200) wild-type neurons contact a mutant hair cell and diameter of the nerve fiber is thinner and shows less branching on the surface of the mutant hair cell than seen in all wild-type cultures
- n seen in all wild-type cultures

increased neuron apoptosis
- at E12 and E14, neuron apoptosis is increased 143% and 155%, respectively, compared to in wild-type mice

small mesencephalic trigeminal nucleus
- approximately half of the neurons are lost from the mesencephalic trigeminal nucleus at P14-16

abnormal cochlear ganglion morphology
- loss of spiral ganglion neurons by 25% at P0 and 29% at P17 in the cochlea

abnormal trigeminal nerve morphology
- mice exhibit a 43% loss of trigeminal neurons at birth

small vestibular ganglion
- approximately 75% of the neurons are lost from the vestibular ganglion at E18.5
- approximately 80% of the neurons are lost from the vestibular ganglion at P14-16
- vestibular neurons appear atrophic

cellular phenotype

increased neuron apoptosis
- at E12 and E14, neuron apoptosis is increased 143% and 155%, respectively, compared to in wild-type mice

craniofacial phenotype

abnormal fungiform papillae morphology
- loss of fungiform papillae is seen in 2 week old mutants and remaining papillae are smaller

Genotype: Bdnf^tm1Jae/Bdnf^tm1Jae
involves: 129S4/SvJae * BALB/c

cellular phenotype

abnormal neuron apoptosis
- cell death in culture following the withdrawal of NGF is delayed
- sympathetic neuron apoptosis is developmentally delayed

nervous system phenotype

abnormal neuron apoptosis
- cell death in culture following the withdrawal of NGF is delayed
- sympathetic neuron apoptosis is developmentally delayed

abnormal neuron morphology
- mice exhibit an increased in sympathetic neuron number (21 318+/-1 627 compared to 15 690+/-617 in wild-type mice) and size

increased neuron number

Genotype: Bdnf^tm1Jae/Bdnf^tm1Jae
B6.129S4-Bdnf

nervous system phenotype

abnormal sensory neuron innervation pattern
- innervation of the fungiform papillae is reduced with a shortfall in the geniculate ganglion neurons that supply taste neurons to the fungiform papillae

taste/olfaction phenotype

abnormal gustatory papillae taste bud morphology
- at P7 homozygous mice have 79% fewer vallate taste buds than wild-type mice

References

Ernfors P; Lee KF; Jaenisch R. 1994. Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature 368(6467):147-50PubMed: 8139657 MGI: J:17123

Additional References

Fan L; Girnius S; Oakley B. 2004. Support of trigeminal sensory neurons by nonneuronal p75 neurotrophin receptors. Brain Res Dev Brain Res 150(1):23-39PubMed: 15126035 MGI: J:90280
Ward NL; Hagg T. 2000. BDNF is needed for postnatal maturation of basal forebrain and neostriatum cholinergic neurons in vivo. Exp Neurol 162(2):297-310PubMed: 10739636 MGI: J:61704

Additional - Bdnf^tm1Jae related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Bdnf
- Standard PCR:Bdnf
- Genotyping resources and troubleshooting
Breeding Considerations

The Bdnf^tm1Jae strain is maintained by mating heterozygous mice to normal wildtype siblings. Heterozygous mice and normal wildtype siblings may be ordered. Expected coat colors from breeding:Black, White Bellied Agouti, Albino
- Additional Breeding and Husbandry Support
Appearance
- black, white-bellied agouti, or albino
  Related Genotype: segregating for a, A^w, and Tyr^c
Citation
When using the BDNF^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002267 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Bdnf<tm1Jae>

Payment Terms and Conditions

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.

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

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

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:BDNF-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Bdnftm1Jae

Allele Symbol: Bdnftm1Jae

Disease Terms

Research Areas By Phenotype

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

Genotype: Bdnftm1Jae related

Mammalian Phenotype Terms by Genotype

Genotype: Bdnftm1Jae/Bdnftm1Jaeinvolves: 129S4/SvJae

behavior/neurological phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

mammalian phenotype

mortality/aging

nervous system phenotype

cellular phenotype

craniofacial phenotype

Genotype: Bdnftm1Jae/Bdnftm1Jaeinvolves: 129S4/SvJae * BALB/c

cellular phenotype

nervous system phenotype

Genotype: Bdnftm1Jae/Bdnftm1JaeB6.129S4-Bdnf

nervous system phenotype

taste/olfaction phenotype

References

Additional References

Additional - Bdnftm1Jae related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:BDNF^-

Bdnf^tm1Jae

Allele Symbol: Bdnf^tm1Jae

Genotype: Bdnf^tm1Jae related

Genotype: Bdnf^tm1Jae/Bdnf^tm1Jae
involves: 129S4/SvJae

Genotype: Bdnf^tm1Jae/Bdnf^tm1Jae
involves: 129S4/SvJae * BALB/c

Genotype: Bdnf^tm1Jae/Bdnf^tm1Jae
B6.129S4-Bdnf

Additional - Bdnf^tm1Jae related