These Slc6a4 knock-out mice may be useful in studying the role of serotonin and serotonin transporter in neurological functions and disorders.
Dennis L Murphy, NIH, NIMH, LCS
Mice that are homozygous for the serotonin transporter targeted mutation (SERT-/- or 5-HTT-/-) are viable and fertile with a superficially unremarkable behavioral phenotype through early adulthood. Serotonin uptake is completely absent in homozygous mice. SERT-deficiency is pleiotropic (many different phenotypic traits). Homozygotes and, to a lesser extent, heterozygotes exhibit diminished responses to serotonin receptor agonists and other classes of drugs (including MDMA, SSRIs, 8-OH-DPAT, and DOI). SERT-mutant mice are also reported to have increased anxiety-like behaviors, altered neuroendocrine and sympathoadrenal responses to even minor stress, diminished aggression, altered emotional learning, substantially increased rapid eye movement (REM) sleep time, reduced brain excitability, increased body temperature, increased colonic motility, reduced spinal reflex to injury, reduced bladder response to stretching, blood pressure responses, diminished bone and muscle strength, reduced physical activity and exercise, and obesity associated with hyperglycemia and increased plasma levels of insulin, leptin, triglycerides and cholesterol. These SERT (or 5-HTT) mutant mice may be useful in studying the role of serotonin and serotonin transporter in behavior and learning, social anxiety, neuropsychiatric and neurological disorders (such as autism), pharmacological actions of therapeutic agents or drugs of abuse, inflammatory bowel disease, obesity and type 2 diabetes and other molecular consequences of SERT inactivation.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector was designed to replace exon 2 of the targeted gene with a PGK-neo cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and the resulting chimeric males were bred with C57BL/6J (and/or CD1) females to generate SERT (or 5-HTT) mutant mice. These mice were subsequently backcrossed to C57BL/6J mice for at least 24-25 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with C57BL/6J for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Klaus-Peter Lesch|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||5-HTT-; 5-HTT KO; SERT -|
|Gene Symbol and Name||Slc6a4, solute carrier family 6 (neurotransmitter transporter, serotonin), member 4|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A neomycin selection cassette replaced a DNA segment containing exon 2. Binding assays on brain sections of adult homozygous mice confirmed that no functional protein was expressed from this allele.|
|Mutations Made By|| |
Klaus-Peter Lesch, University of W¿rzburg
When maintaining a live colony, heterozygous or homozygous mice may be bred. The donating investigator breeds heterozygous females with homozygous males, and recommends monitoring litter frequency and sizes as the high anxiety observed in homozygous (and to a lesser extent heterozygous) females may result in undesirable maternal behaviors. The donating investigator also notes better breedings results if mice are placed in matings at no less than 8 weeks of age.
When using the 5-HTT- mouse strain in a publication, please cite the originating article(s) and include JAX stock #008355 in your Materials and Methods section.
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