Exon 1b of the mouse Ank3 (AnkG) gene is disrupted to create a knock-out of the cerebellar isoform. Homozygous mutant mice exhibit a progressive ataxia beginning around postnatal day P16 and subsequent loss of Purkinje neurons.
Vann Bennett, Duke University Medical Center
Exon 1b of the mouse Ank3 (ankyrin 3, epithelial; also called AnkG) gene is strongly expressed in the cerebellum, but it is also detectable in the brain stem and thalamus at low levels. A neomycin cassette was introduced to the exon to create a knock-out of the associated cerebellar isoform. No exon 1b-containing transcripts are detected in the homozygous mutant mice, and expression levels of transcripts containing exon 1e are unaffected.
Homozygous mutant mice are born in nearly Mendelian ratios and exhibit a progressive ataxia beginning around postnatal day P16 and subsequent loss of Purkinje neurons. This phenotype is reported to have a variable onset and severity. In mutant mouse cerebella, voltage-gated sodium channels (NaCh) are absent from axon initial segments of granule cell neurons, and Purkinje cells show deficiencies in their ability to initiate action potentials and support rapid, repetitive firing. Neurofascin, a member of the L1CAM family of ankyrin-binding cell adhesion molecules, as well as beta-4 spectrin (Sptbn4) and KCNQ2/3 channels also exhibit impaired localization to initial segments of Purkinje cell neurons. In addition, ponceau synapses of GABAergic neurons are absent at the axon initial segment. Results suggest that this gene is essential for assembly of axon initial segments and is required for physiological levels of sodium channel activity. Some premature death of homozygous mice may occur between 4 and 6 months of age, and in some cases may be preceded by uncontrollable jumping and convulsions. Although homozygotes are fertile, they do not breed well. Heterozygotes are phenotypically normal. PMID 9832557)
A neomycin cassette was introduced to a SmaI restriction site within exon 1b via homologous recombination in (129X1/SvJ x 129S1/Sv)F1- Kitl+-derived R1 embryonic stem (ES) cells. Resultant chimeric males were crossed with C57BL/6J females. This strain was backcrossed to a C57BL/6 inbred strain for 10 generations by the donating laboratory.
|Allele Name||targeted mutation 1, Vann Bennett|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Ank3tm1Bnt; targeted mutation 1, Vann Bennett|
|Gene Symbol and Name||Ank3, ankyrin 3, epithelial|
|Gene Synonym(s)||ankyrin 3, brain; ANK-3; AnkG; expressed sequence AI314020; ANKYRIN-G; RIKEN cDNA 2900054D09 gene; Ank-3; Ankyrin-3; AI314020; MRT37; 2900054D09Rik; 2900054D09Rik; Ank-3; Ankyrin-G|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A neomycin resistance cassette was inserted into exon 1b, which is an alternatively spliced exon found in transcripts only in brain. Northern blot analysis on RNA derived from homozygous brains demonstrated that no transcript containing exon 1b was expressed, while expression of transcripts containing other alternaltively spliced exons remained unaffected. Western blot analysis and immunohistochemistry experiments confirmed that little or no protein was seen in cerebellum.|
Heterozygotes are viable and fertile. Although homozygotes are fertile, they do not breed well.
When using the exon1b-null mouse strain in a publication, please cite the originating article(s) and include JAX stock #029799 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.