These Pink1 knockout mice exhibit reduced mean evoked dopamine overflow, altered dopamine signaling, and have applications in studies related to Parkinson's disease.
Jie Shen, Harvard Med Sch/Brigham Women's Hosp
These Pink1 (PTEN induced putative kinase 1) knockout mice have exons 4 through 7 deleted, disrupting most of the kinase domain and producing a nonsense mutation at the start of exon 8 due to a reading frame shift. Missense mutations in the PINK1 gene cause autosomal-recessive Parkinson's disease. PINK1 loss of function results in mitochondrial dysfunction, increased reactive oxygen species production and calcium homeostasis imbalance. Homozygous mutant mice are viable and fertile. No Pink1 mRNA is detected by Northern blot analysis in brain tissue from homozygotes. Evoked release of striatal dopamine and catecholamine, and catecholamine release by adrenal chromaffin cells is decreased in homozygotes. Dopamine levels in the striatum, dopaminergic neuron number, dopamine synthesis and dopamine receptor number are not altered. Homozygotes exhibit impaired induction of long-term potentiation and long-term depression at corticostriatal synapses. No nigrostriatal neurodegeneration is detected in homozygous mice 9 months of age. Homozygotes are more sensitive to metabotropic glutamate (mGlu) receptor agonist than wildtype controls.
A targeting vector containing a PGK-NEO cassette was used to disrupt exons 4 through 7. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to generate homozygotes. The mice were then backcrossed to C57BL/6J for 7 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, Jie Shen|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||targeted mutation 1, Jie Shen; Pink1tm1Shn|
|Gene Symbol and Name||Pink1, PTEN induced putative kinase 1|
|Gene Synonym(s)||RIKEN cDNA 1190006F07 gene; BRPK; 1190006F07Rik; expressed sequence AW557854; expressed sequence AU042772; AU042772; AW557854; PARK6; 1190006F07Rik; brpk|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Exons 4-7 were replaced with a pgk-neo cassette via cre mediated recombination, thereby removing the majority of the kinase domain and creating a nonsense mutation at the beginning of exon 8. Northern blot confirmed absence of transcript in mutants.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Pink1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #017946 in your Materials and Methods section.
|Heterozygous or wildtype for Pink1<tm1Shn>|
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.
"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.