Slc12a6 is a member of the solute carrier family that encodes the K+/Cl- cotransporter 3 (KCC3 or SLC12A6). KCC3 has a role in ion homeostasis and is associated with the neurodevelopmental and neurodegenerative disorder called hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC). Most HMSN/ACC patients carry a deletion in exon 18 (a conserved splice donor site) that results in a stop codon at position 813 (Thr813X). KCC3 is expressed in brain, kidney, muscle lung and heart.
These mutant mice possess loxP sites flanking exon 18 of the Slc12a6 gene. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express Cre recombinase, the resulting offspring will have exon 18 deleted in the cre-expressing tissues resulting in a C terminal truncation of the protein mimicking the human HMSN/ACC mutation. These mice may be useful in generating conditional knockouts for studying the role of KCC3 in the central and peripheral nervous systems.
For example, when bred to mice carrying Tg(Syn1-cre)671 Jxm (see Stock No. 003966), Cre recombinase expression in neuronal cells results in hyperactivity, reduced pain sensitivity, axonal degeneration, axon swelling, and hypoplasia of the corpus callosum.
