This knockout mutant of the Pdcd4 (programmed cell death 4) gene exhibits reduced cytokine secretion, lower susceptibility to LPS challenge and EAE, resistance to STZ- induced diabetes, and develops spontaneous lymphoma.
Youhai Chen, University of Pennsylvania
The programmed cell death 4 protein is a proinflammatory agent and tumor suppressor that also inhibits translation initiation and cap-dependent translation. MicroRNA-21 (miR-21) downregulates Pdcd4 expression post-translationally.
Mice homozygous for this knockout mutation of Pdcd4 are viable and fertile, however 86% of homozygotes die due to lymphoma by 106 weeks of age (mean life expectancy of homozygotes is reduced to 101 weeks). At approximately 20 months of age, many homozygotes develop spontaneous lymphoma (primarily diffuse B cell), often with metastasis to liver and kidney. Approximately half of homozygotes at 20 weeks of age exhibit kidney, ovary, or prostate cysts. No Pdcd4 mRNA or protein is detected by Northern or Western blot analysis of thymus. Homozygotes are resistant to STZ (streptozotocin) induced diabetes (5% compared to 59% in controls), and exhibit reduced severity and mortality of EAE (experimental autoimmune encephalomyelitis). IL-4, IL-10, and
IFNG cytokine secretion is elevated in homozygous animals. Homozygotes display reduced susceptibility to and lower circulating IL-6 levels after lipopolysaccharide (LPS) challenge, and lower resulting mortality compared to wildtype controls. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6J genetic background.
A targeting vector containing a neomycin resistance gene was used to disrupt exons 3 and 4. The construct was electroporated into 129S6/SvEvTac derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting male chimeric animals were crossed to C57BL/6J female mice, and then backcrossed to C57BL/6 for at least 5 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Youhai H Chen|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Pdcd4tm1Yhcn; targeted mutation 1, Youhai H Chen|
|Gene Symbol and Name||Pdcd4, programmed cell death 4|
|Gene Synonym(s)||Dug; D19Ucla1; TIS; H731; DNA segment, Chr 19, University of California at Los Angeles 1; MA-3; D19Ucla1|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||A targeting vector was designed to replace exons 3 and 4 with a neomycin resistance cassette. Absence of protein was confirmed in mutant lymphoid organs.|
|Mutations Made By|| |
Youhai Chen, University of Pennsylvania
When maintaining a live colony, these mice can be bred as homozygotes, however 86% of homozygotes die by 106 weeks of age (mean life expectancy of homozygotes is reduced to 101 weeks).
When using the B6.129S6-Pdcd4tm1Yhcn/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018164 in your Materials and Methods section.
"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.