This model of X-linked congenital stationary night blindness has a more severe phenotype that that of the Cacna1fnob2 mutation in AXB6/PgnJ. Degeneration of the outer plexiform layer begins by 14 days of age and progresses rapidly with ERG readings being greatly diminished by 1 month of age.Read More +
This spontaneous G to A substitution in the intron just before exon 14 created a novel CAG splice acceptor site resulting in the inclusion of 10 base pairs of intronic sequence into the 5-prime end of exon 14, which yields a frameshift and premature termination. This mutation provides a model for X-linked type 2A congenital stationary night blindness (CSNB2A). The outer plexiform layer appears to develop normally with near normal thickness at 10 days of age, but degenerates early, with diminished thickness by 14 days of age, progressing such that it is almost absent between 2 and 8 months of age. By 8 months of age small white dots are found in the fundus, mainly in the central and ventral quadrants. Homozygotes display a drastically reduced scotopic ERG. At 1 month of age the scotopic ERG shows a greatly diminished, but not absent, b-wave, which displays small oscillatory potentials. The a-wave amplitude is approximately half that of wild-type controls at 2 months of age and this degrades with age until the amplitude is approximately 27% that found in controls at 14 months of age. Photopic ERGs show drastic reduction in response, with almost no waveform by 2 months of age. At 2 months of age both S-opsins and M-opsins are present in the retinas at normal levels, but both decline with age, with the loss of M-opsins being more severe such that at 14 months of age there remain almost no M-opsins and only 54% of normal levels of S-opsins and those were found to abnormally localized to the inner photoreceptor segments. ERGs with white light, green light, and UV light failed to elicit an ERG response at 2, 8, and 14 months of age. Compared with the Cacna1fnob2 mutation characterized in the AXB6/PgnJ recombinant inbred strain, the Cacna1fnob9 mutation has a faster disease onset and more severe phenotype.
The no b-wave 9 mutation was first identified in the C57BL/6J-Chr 10.3PWD/Ph/ForeJ strain by Dr. Bo Chang at The Jackson Laboratory. A mutant male was bred to C57BL/6J and the offspring, which were all phenotypic wild-type, were intercrossed, producing 12 wild-type females, 3 wild-type males, and 4 mutant males, indicative of a recessive X-linked mutation. This mutation was then backcrossed from mutant males to C57BL/6J females until the strain reached generation N5, at which point the maintenance of the strain changed to sibling intercrossing and eventually became homozygous females bred to hemizygous males. This strain reached generation N5F21 in 2018.
|Allele Name||no b wave 9|
|Allele Type||Spontaneous (Not Specified)|
|Gene Symbol and Name||Cacna1f, calcium channel, voltage-dependent, alpha 1F subunit|
|Strain of Origin||C57BL/6J-Chr 10.3PWD/Ph/ForeJ|
|Molecular Note||This spontaneous mutation involves an intronic G-to-A substitution, which creates a novel CAG splice acceptor site. Use of this ectopic acceptor creates a mis-spliced transcript with a 10 bp 5' extension of exon 14 that results in a frameshift and premature stop codon.|
"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.