This point mutation occurred in a conserved residue of the extracellular loop 2 motif, which is important in docking selectivity for interactions with other connexins and thereby important in gap junction formation. This mutation is semidominant, causing dense nuclear cataracts evident by 3 weeks of age in both heterozygotes and homozygotes, and microphthalmia only in homozygotes. Lens epithelial cells do not display the typical mosaic pattern, and suture formation of the lens is aberrant in homozygotes. Dampened trans-junctional conductance in paired oocyte expression of this mutant connexin, co-expressed with wild-type GJA8 or GJA3, supports the hypothesis that this mutation functions as a dominant negative. When this mutation is backcrossed onto the C57BL/6J background congenic heterozygotes have normal sized eyeballs, slightly smaller than normal lenses, and very mild nuclear cataracts while homozygotes have microphthalmia with lenses much smaller than normal, dense nuclear cataracts and vacuole-like structures in the lens periphery. This is a more severe phenotype than that of Gja8tm1Scr homozygotes. The disruption of peripheral lens fiber cells to form the vacuole-like structures was found to require Gja3, but the microphthalmia and cataract phenotypes do not.
The Gja8R205G mutation arose spontaneously in the CWXS/Agl recombinant inbred line in the laboratory of Dr. Joe Angel at The University of Texas and was sent to Dr. Bo Chang at The Jackson Laboratory for characterization in 1995. It was maintained on this recombinant inbred background by sibling breeding and sperm was cryopreserved from homozygous males in 2012. This bankstock will be cryo-recovered using C57BL/6J oocytes so the genetic background will be a mixture of CWD/LeAgl, SJL/J, and C57BL/6J. Pups generated by cryorecovery using C57BL/6J oocytes have been proven to display the expected cataract phenotype.
|Gene Symbol and Name||Gja8, gap junction protein, alpha 8|
|Strain of Origin||CWXS/Agl|
|Molecular Note||A spontaneous C-to-G point mutation results in the amino acid substitution of arginine with glycine at position 205 (p.R205G).|
"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.