Exons 3-5 of the mouse Atraid (TBONE) gene are flanked by loxP sites in this lacZ reporter-tagged conditional mutant strain. Cre-mediated excision of the floxed region results in a knockout allele useful in studies of osteoporosis and nitrogenous bisphosphate (NBP) therapies.
Erin O'Shea, Harvard University
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Conditional ready (e.g. floxed), Reporter, Null/Knockout) | Atraid | all-trans retinoic acid induced differentiation factor |
Nitrogenous bisphosphates (NBPs), having an anti-proliferative effect on cells, are commonly-prescribed for the treatment of osteoporosis. Target of BisphOsphonate NitrogEnous (TBONE; formal name Atraid, all-trans retinoic acid induced differentiation factor) is a novel NBP target gene required for the molecular and cellular effects of NBPs on bone. It is a founding component of a mineralization-regulating and mammalian nitrogenous phosphonate-sensing pathway.
Exons 3-5 of the TBONE/Atraid gene are flanked by loxP sites in this lacZ reporter-tagged conditional mutant strain. Cre-mediated excision of the floxed region results in a knockout allele.
Homozygous knockout mice, created through crosses with CMV-cre animals, are viable but have low body mass, deregulated markers of bone remodeling and impaired therapeutic responses to Alendronate (a drug used to treat osteoporosis). Basal levels of the active (nuclear) form of NFATC1 protein, essential for the formation of both osteoblasts and osteoclasts, are reduced and calcium-induced nuclear accumulation is strongly diminished. As judged by markers of calcium (Alizarin Red) and phosphate (Von Kossa) precipitation, TBONE knockdown strongly impairs osteoblast differentiation. Evidence suggests that naturally occurring nitrogenous phosphonates (NPs) regulate mineralization in a TBONE-dependent manner and TBONE is critical for the anti-resorptive effects of NBPs on bone in mice.
As 11/2014, the lacZ reporter component of this allele has not yet been tested.
Embryonic stem (ES) cell clone HEPD0577_2_D01 (IMPC Product: 72859) was created as part of the Knockout Mouse Project (KOMP). This gene-trapped allele of Atraid incorporates an FRT-En2 splice acceptor (SA)-IRES-lacZ-SV40 polyadenylation signal (pA)-loxP-hbactP-Neo-pA-FRT-loxP sequence in intron 2 of the gene and an additional loxP site in intron 5 to create the “knockout first” (tm1a(EUCOMM)Hmgu) allele. C57BL/6N-Atm1Brd-derived JM8A1.N3 embryonic stem (ES) cells were used to create the mutation. This strain was backcrossed to C57BL/6J for 2 generations by the donating laboratory.
Allele Name | targeted mutation 1a, Helmholtz Zentrum Muenchen GmbH |
---|---|
Allele Type | Targeted (Conditional ready (e.g. floxed), Reporter, Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Atraid, all-trans retinoic acid induced differentiation factor |
Gene Synonym(s) | |
Strain of Origin | C57BL/6N-Atm1Brd |
Chromosome | 5 |
Molecular Note | The L1L2_Bact_P cassette was inserted at position 31051591 of Chromosome 5 upstream of the critical exon(s) (Build GRCm38). The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by a neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site is inserted downstream of the targeted exon(s) at position 31053173. The critical exon(s) is/are thus flanked by loxP sites. A "conditional ready" (floxed) allele can be created by flp recombinase expression in mice carrying this allele. Subsequent cre expression results in a knockout mouse. If cre expression occurs without flp expression, a reporter knockout mouse will be created. Further information on targeting strategies used for this and other IKMC alleles can be found at http://www.informatics.jax.org/mgihome/nomen/IKMC_schematics.shtml |
Heterozygous and homozygous floxed mice are viable and fertile.
When using the C57BL/6-Atraidtm1a(EUCOMM)Hmgu/EosJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #026576 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Atraid<tm1a(EUCOMM)Hmgu> |
Frozen Mouse Embryo | C57BL/6-Atraid<tm1a(EUCOMM)Hmgu>/EosJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Atraid<tm1a(EUCOMM)Hmgu>/EosJ Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C57BL/6-Atraid<tm1a(EUCOMM)Hmgu>/EosJ Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | C57BL/6-Atraid<tm1a(EUCOMM)Hmgu>/EosJ Frozen Embryo | $3373.50 |
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 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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.