These CskAS mice express a conditionally inhibitory CSK protein and lack endogenous CSK expression. They may be useful for studying the requirements of Csk on the control of TCR signaling.
Dr. Arthur Weiss, University of California, San Francisco
|Allele Type||Gene Symbol||Gene Name|
|Targeted||Csk||c-src tyrosine kinase|
|Transgenic (Inserted expressed sequence)|
Mice hemizygous for the BAC CskAS transgene are viable and fertile. These mice do not express the endogenous c-src tyrosine kinase (CSK) protein. These mice do express mutant CSK, from the BAC transgene, which contains a point mutation at position 266 resulting in a threonine to glycine mutation. This mutation creates a larger ATP-binding pocket in the expressed protein, allowing for specific and rapid inhibition by an analog of the kinase inhibitor PP1, 3-iodo-benzyl-PP1 (3-IB-PP1). CSK is a cytosolic tyrosine-protein kinase that plays a role in the regulation of cell growth, differentiation, migration and immune response. CSK phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs), which in turn suppress signaling by surface receptors including T-cell receptor (TCR) and B-cell receptor (BCR). CskAS mice have 2.5-fold as much expression of CSK as wild-type mice and display normal T cell development. Inhibition of CSK with 3-IB-PP1 in thymocytes induces activation of SFKs and proximal TCR signaling. Defects in inositol phosphates, intracellular calcium, and phosphorylation of Erk are also seen, although remodeling of the actin cytoskeleton is sufficient to reverse these defects and to allow full TCR signaling. Mice hemizygous for the CSK* transgene and homozygous for Csktm1Sor allele are viable and fertile. The Csktm1Sor allele alone is homozygous embryonic lethal. The donating investigator has not tried to make CSK* transgenic homozygous mice.
Bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a BAC (#RP24-400B5) containing the entire mouse Csk (c-src tyrosine kinase) gene. A point mutation was introduced in Csk at position 266 resulting in a threonine to glycine mutation, inducing a larger ATP-binding pocket to be formed in the expressed protein. To inactivate other genes present in the BAC, both ends of the BAC were deleted, leaving 74kb of sequence, and an in-frame stop codon was inserted in exon 2 of Lman1l (lectin, mannose-binding 1 like) gene. This BAC was microinjected into fertilized C57BL/6 oocytes. CskAS mice from founder line 2 were maintained by breeding transgenic mice with mice carrying the Csktm1Sor/J allele that have been bred to C57BL/6 mice for at least 13 generations (similar to Stock No. 003201). These mice were maintained on a C57BL/6 background. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Expressed Gene||Csk, c-src tyrosine kinase, mouse, laboratory|
|Site of Expression|
|Allele Name||targeted mutation 1, Philippe Soriano|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Csk, c-src tyrosine kinase|
|Gene Synonym(s)||AW212630; expressed sequence AW212630|
|Strain of Origin||129S7/SvEvBrd-Hprt<+>|
|Mutations Made By|| |
Dr. Philippe Soriano, Mount Sinai School of Medicine
|Allele Name||transgene insertion 2, Arthur Weiss|
|Allele Type||Transgenic (Inserted expressed sequence)|
|Gene Symbol and Name||Tg(Csk*)2Weis, transgene insertion 2, Arthur Weiss|
|Promoter||Csk, c-src tyrosine kinase, mouse, laboratory|
|Expressed Gene||Csk, c-src tyrosine kinase, mouse, laboratory|
|Strain of Origin||C57BL/6|
When maintaining a live colony, mice hemizygous for the CSK* transgene and homozygous for Csktm1Sor may be bred to mice heterozygous for Csktm1Sor, or to wildtype mice from the colony, or to C57BL/6J (Stock No. 000664). The Csk
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.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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.
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.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.