The VGFflpflox allele has loxP sites flanking the VGF nerve growth factor inducible coding region. Removal of the floxed sequence creates a null allele. These mice may be useful for generating tissue-specific VGF-deletion for studying neuronal activity, survival and progenitor proliferation, synaptic plasticity (fear and spatial memory), BDNF/TrkB-signaling and regulating energy homeostasis/metabolism.
Stephen RJ Salton, Icahn School of Medicine at Mount Sinai
The VGF protein (encoded by the VGF nerve growth factor inducible gene) is a BDNF-inducible neuropeptide precursor and secreted granin protein that is proposed to play a role in regulating energy homeostasis, metabolism and synaptic plasticity. In the CNS, VGF-derived peptides regulate neuronal activity, survival and progenitor proliferation. The C-terminal VGF-derived peptides enhance neuronal transmission through a BDNF-TrkB-dependent pathway in hippocampal slices. In addition, full-length VGF functions in the regulated secretory pathway, modulating formation of large dense-core vesicles (LDCVs).
The VGFflpflox allele has loxP sites flanking the VGF coding region. Mice homozygous for this floxed allele (VGFflpflox/flpflox) are viable and fertile, express normal levels of VGF and have no reported gross physical or behavioral abnormalities.
When bred to mice that express Cre recombinase, the resulting offspring will have the floxed region deleted in cre-expressing tissues; creating the knock-out allele (VGFnull).
For example, when VGFflpflox are bred to have the αCaMKII-Cre transgene (Stock No. 005359), the resulting VGF ablation in adult forebrain excitatory neurons results in memory impairments.
Furthermore, when VGFflpflox are bred to have pan-neuronal Cre expression starting ~E12 (via breeding to Synapsin-Cre transgenic mice; Stock No. 003966), the resulting VGF-deficiency results in significantly reduced body weight, increased energy expenditure and resistance to diet-induced obesity.
Of note, when VGFflpflox are bred to germline Cre-expressing mice, the resulting global null homozygotes may be expected to exhibit a similar phenotype as published conventional knock-out mice (i.e., lean, hypermetabolic and infertile, as well as resistant to diet-, lesion-, and genetically-induced obesity and diabetes).
The VGFflpflox mice were created by Dr. Stephen R.J. Salton (Icahn School of Medicine at Mount Sinai). A targeting vector was designed to insert a loxP site in exon 2, and a second loxP site followed by a frt-flanked reverse-oriented PGK-neo cassette just downstream of the coding region in exon 3 of the VGF nerve growth factor inducible locus (Vgf) on chromosome 5. The donating investigator reports the construct was electroporated into hybrid (129 x C57BL/6) embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric males were bred to C57BL/6J females for germline transmission. Offspring were bred with C57BL/6J.FlpE-deleter mice (from Stock No. 009086) for germline deletion of the PGK-neo cassette, resulting in mice with the VGFflpflox allele. The VGFflpflox colony was backcrossed to C57BL/6J wildtype mice for five generations (and the FlpE-deleter allele was removed). In 2012, heterozygous males with black coat color (>98% C57BL/6J) were sent to The Jackson Laboratory Repository. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm may be used to fertilize C57BL/6J oocytes (Stock No. 000664).
Of note, the donating investigator reports that, at least once during backcrossing, a VGFflpflox female was bred to a C57BL/6J inbred male (thus the Y chromosome of the congenic strain is of C57BL/6J origin).
|Allele Name||targeted mutation 4.1, Stephen R J Salton|
|Allele Type||Targeted (Conditional ready (e.g. floxed))|
|Allele Synonym(s)||Vgftm4.1Srjs; targeted mutation 4.1, Stephen R J Salton|
|Gene Symbol and Name||Vgf, VGF nerve growth factor inducible|
|Gene Synonym(s)||Gm1052; LOC381677; gene model 1052, (NCBI); SgVII; SCG7|
|Strain of Origin||(C57BL/6NTac x 129S6/SvEvTac)F1|
|Molecular Note||A loxP site was inserted into the 5'UTR. Flp-mediated recombination removed an FRT-flanked neomycin resistance cassette with a 3' loxP site inserted into the 3' UTR.|
When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). Alternatively, homozygous mice may be bred together.
When using the Vgfflpflox mouse strain in a publication, please cite the originating article(s) and include JAX stock #030571 in your Materials and Methods section.
|Heterozygous or wildtype for Vgf<tm4.1Srjs>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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