These "super-smeller" mice carry a knockout allele of Kcna3 which lowers the threshold for detection of odors, increases the ability to discriminate between odors, and alters the firing pattern of mitral cells.
Leonard K Kaczmarek, Yale University School of Medicine
Kv1.3 (Kcna3, potassium voltage-gated channel, shaker-related subfamily, member 3) is a voltage-gated potassium channel that has roles in T cell activation/proliferation, cell-mediated cytotoxicity, and volume regulation. It is also expressed at high levels in mitral cells of the olfactory bulb (OB).
These mice carry a targeted knockout of Kcna3. Knockout of the gene lowers the threshold for detection of odors, increases the ability to discriminate between odors, and alters the firing pattern of mitral cells. Loss of Kv1.3 produces a compensatory increase in Na+-activated K+ currents (KNa) in mitral cells of these “super-smeller” mice.
Elimination of the Kv1.3 voltage-dependent potassium channel gene produces striking changes in the function of the olfactory bulb, raising the possibility that this channel also influences other sensory systems. The finding of a tonotopic gradient in presynaptic terminals suggests that Kv1.3 may regulate neurotransmitter release differentially in neurons that respond to different frequencies of sound.
The majority of thymocytes from knockout mice have no detectable voltage-dependent potassium current, but the chloride current is increased approximately 50-fold over that of wildtype cells. There are no abnormalities in lymphocyte types or absolute numbers in thymus, spleen, and lymph nodes and no obvious defect in thymocyte apoptosis or T cell proliferation in the homozygous knockout animals. The compensatory effects of the enhanced chloride current may account for the apparent lack of immune system defects in these mice.
The promoter region and the 5' end of the coding region were replaced by a neomycin resistance gene in inverse orientation. The mutation was created through homologous recombination in 129S1/Sv-Oca2+Tyr+Kitl+-derived W9.5 embryonic stem (ES) cells. Resultant chimeric males were bred to C57BL/6 females. This line was maintained on a mixed C57BL/6 and 129 background by the donating laboratory.
|Allele Name||targeted mutation 1, Lyanne C Schlichter|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Kcna3, potassium voltage-gated channel, shaker-related subfamily, member 3|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||The promotor region and the 5' end of the coding region were replaced by a neomycin resistance gene in inverse orientation. Absence of mRNA transcripts was demonstrated by RT-PCR and absence of protein product by Western blot.|
Homozygotes are viable and fertile.
When using the KV1.3-deficient mouse strain in a publication, please cite the originating article(s) and include JAX stock #027392 in your Materials and Methods section.