Homozygous Ank2 knockout mice exhibit hypoplasia of the corpus callosum and pyramidal tracts, dilated ventricles, extensive degeneration of the optic nerve, and they die by postnatal day 21. These mice share features of human patients with L1CAM mutations.
Vann Bennett, Duke University Medical Center
Mice are typed using a generic neo assay. At this time the allele specific assay has not been working for this strain.
Ank2 (ankyrin 2, brain) and L1cam (L1 cell adhesion molecule) interaction is essential for maintenance of pre-myelinated axons in vivo.
These mice carry a targeted knockout of the mouse Ank2 gene. Homozygotes exhibit a phenotype similar to, but more severe, than L1cam knockout mice (e.g. Stock No. 003120) and share features of human patients with L1CAM mutations.
Mice exhibit hypoplasia of the corpus callosum and pyramidal tracts, dilated ventricles, extensive degeneration of the optic nerve, and they die by postnatal day 21. Homozygotes have a reduced L1CAM in pre-myelinated axons of long fiber tracts, including the corpus callosum, fimbria, and internal capsule in the brain, and pyramidal tracts and lateral columns of the spinal cord. L1CAM is detectable in the optic nerve at postnatal day 1, but disappears by postnatal day 7. Optic nerve axons become dilated and diameters are up to eightfold greater than normal, but degenerate by day 20.
Brains of knockout mice exhibit a nearly complete loss of a major 13-kb mRNA transcript encoding the 440 kD protein, as well as a loss of less abundant 8 and 5 kb transcripts encoding 220 and 150 kD polypeptides, respectively. The 440 and 220 kD polypeptides are undetectable in brain homogenates assayed by immunoblot. A minor 150 kD polypeptide, which lacks a membrane binding domain, is still barely detectable.
Homozygous mice are born at nearly Mendelian ratios, however, over half of the homozygotes are moribund or dead on the first postnatal day, and 95% by postnatal day 8. Very few survive until postnatal day 20. Those that survive until 2 weeks of age are approximately 25% of the weight of wildtype littermates, and exhibit abnormal locomotion and balance.
A neomycin resistance cassette, an in-frame hemagglutinin (HA) epitope, and a stop codon were introduced to exon 22 to disrupt the spectrin binding domain. The mutation was created via homologous recombination in 129-derived embryonic stem cells. Resultant male chimeric mice were bred with C57BL/6J females. This strain was maintained on a mixed 129 and C57BL/6J genetic background by the donating lab.
|Allele Name||targeted mutation 1, Vann Bennett|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||AnkyrinB -|
|Gene Symbol and Name||Ank2, ankyrin 2, brain|
|Strain of Origin||129|
|General Note||Phenotypic Similarity to Human Syndrome: Sinoatrial (SAN) disease (J:163867)|
|Molecular Note||A neomycin resistance gene, an in-frame HA epitope and a stop codon were inserted into the exon encoding the spectrin binding domain. Northern blot analysis on RNA derived from homozygous brains demonstrated that no detectable transcript was expressed from this allele. Western blot analysis on homogenates of homozygous brain confirmed that no encoded protein was present.|
Heterozygotes are viable and fertile. Homozygotes die by postnatal day 21.
When using the AnkyrinB - mouse strain in a publication, please cite the originating article(s) and include JAX stock #027916 in your Materials and Methods section.
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