B6.129(C)-Bdnf^tm1.1Bail/KmrtJ

Stock number: 033943
Product name: Bdnf-e4
Research areas: Cell Biology Research, Neurobiology Research

Description

Bdnf-e4^-/- mice have an EGFP-STOP cassette inserted upstream of the splice donor site of exon 4 of the brain derived neurotrophic factor (Bdnf) gene. These mice may be useful when studying the functional role of BDNF production from unique promoters in aggression and serotonin signaling.

Detailed description

Bdnf-e4^-/- mice have an EGFP-STOP cassette inserted upstream of the splice donor site of exon 4 of the brain derived neurotrophic factor (Bdnf) gene that results in disruption of production of BDNF from promoter 4, while leaving expression of BDNF from other promoters intact. During development, BDNF promotes the survival and differentiation of selected neuronal populations where it participates in axonal growth, pathfinding, and in the modulation of dendritic growth and morphology. It is a major regulator of synaptic transmission and plasticity at adult synapses in many regions of the central nervous system (CNS). BDNF contributes to a range of adaptive neuronal responses including long-term potentiation (LTP), long-term depression (LTD), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability. Loss of expression of this gene is associated with neurobehavioral alterations and several neuropsychiatric disorders including Alzheimer's, Parkinson's, and Huntington's disease.

BDNF transcription is regulated by nine individual promoters, which drive expression of protein variants. Bdnf-e4 expression in these mice is decreased in the hypothalamus, prefrontal cortex, and hippocampus. These mutant mice are not aggressive. However, deficits in hippocampal-prefrontal signaling that are associated with processing of fear learning and memory have been identified. They have decreases in the expression of GABAergic interneuron markers such as cortistatin (Cort), somatostatin (Sst), corticotropin-releasing factor-binding protein (Crhbp), and tachykinin (Tac1).

Homozygous mice are viable and fertile.

Of note, similar strains with BDNF transcription selectively disrupted from one of the other major promoters are available:
Bdnf-e1^-/- mice, with transcription from exon 1 disrupted, are available as Stock No. 033941.
Bdnf-e2^-/- mice, with transcription from exon 2 disrupted, are available as Stock No. 033942.
Bdnf-e6^-/- mice, with transcription from exon 6 disrupted, are available as Stock No. 033944.

Development

The Bdnf-e4^-/- targeting vector was designed to insert an enhanced green fluorescent protein (EGFP)-STOP cassette, followed by a loxP-flanked neomycin selection cassette (neo) in reverse orientation, upstream of the splice donor site of exon 4 of the brain derived neurotrophic factor (Bdnf) gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to CMV-Cre mice (Stock No. 006054) mice to remove the neo cassette. Resulting Bdnf-e4^-/- males were bred to C57BL/6J mice for at least 12 generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Bdnf^tm1.1Bail
Name: targeted mutation 1.1, Bai Liu
MGI accession ID: MGI:6378539
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Synonyms: Bdnf-e4^-
Marker symbol: Bdnf
Marker name: brain derived neurotrophic factor
Marker synonyms: ANON2; BULN2
Chromosome: 2
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Site of expression: Brain and spinal cord.
Molecular note: An enhanced green fluorescent protein (EGFP)-STOP cassette, followed by a loxP-flanked neomycin selection cassette (neo) in reverse orientation was inserted 3' of the promoter IV exon. Cre-mediated recombination removed the upstream floxed neo cassette.