These mal KO mice carry a knock-out allele of the mouse Mal (myelin and lymphocyte protein, T cell differentiation protein) gene, useful in studies of axon-glia interactions in the central nervous system. A lacZ/neo reporter replaces a portion of exon 1.
Nicole Schaeren-Wiemers, University Hospital Basel
The myelin and lymphocyte gene (Mal) encodes a tetraspan raft-associated proteolipid predominantly expressed by oligodendrocytes and Schwann cells. MAL protein is also involved in the apical delivery of fusiform vesicles in urothelial umbrella cells, and is required for the binding and activity of Clostridium perfringens e-Toxin which causes selective death of mature oligodendrocytes and central nervous system demyelination.
These mice carry a targeted knockout of the mouse Mal gene. LacZ/neo was inserted after the third codon in exon 1, and replaces the remainder of exon 1. Northern blot indicates a lack of full-length transcript in homozygotes, but presence of a lacZ-containing transcript in homozygotes and heterozygotes. Absence of wild-type protein has been demonstrated by immunohistochemical assay of sciatic nerves and brain from mutants.
Homozygous knock-out of Mal results in cytoplasmic inclusions within compact myelin, paranodal loops that are everted away from the axon and disorganized transverse bands at the paranode-axon interface in the adult CNS. These structural changes are accompanied by a marked reduction of CASPR, Neurofascin 155 (NAFASC; NF155) and the potassium channel Kv1.2 (KCNA2), while nodal clusters of sodium channels are unaltered. Initial formation of paranodal regions appears normal, but abnormalities become detectable when MAL is starting to be expressed. Biochemical analysis has revealed reduced MAG, MBP and NF155 protein levels in myelin and myelin-derived rafts. Results demonstrate a critical role for MAL in the maintenance of CNS paranodes, likely by controlling the trafficking and/or sorting of NF155 and other membrane components in oligodendrocytes.
LacZ/neo was inserted in frame after the third codon in exon 1 (replacing the remainder of exon 1) via homologous recombination in 129P2/OlaHsd-derived embryonic stem cells. Resultant mice were backcrossed to C57BL/6J by the donating laboratory.
|Allele Name||targeted mutation 1, Nicole Shaeren-Wiemers|
|Allele Type||Targeted (Reporter, Null/Knockout)|
|Gene Symbol and Name||Mal, myelin and lymphocyte protein, T cell differentiation protein|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A lacZ/neo cassette was inserted in frame after the third codon in exon 1, replacing the remainder of exon 1. Southern blot confirmed recombination in mutant mice. Northern blot indicated a lack of full-length transcript in homozygotes, but presence of a lacZ-containing transcript in homozygotes and heterozygotes. Absence of wild-type protein was demonstrated by an immunohistochemistry assay of sciatic nerves and brain from mutants.|
Heterozygotes and homozygotes are viable and fertile.
When using the Mal- mouse strain in a publication, please cite the originating article(s) and include JAX stock #032534 in your Materials and Methods section.
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