These 5-HT7 receptor-deficient mice exhibit impaired learning, memory, behavior and sleep patterns. They may be suitable for applications involving the study of synaptic plasticity, circadian rhythms as well as depression and obsessive-compulsive disorder.
Peter Hedlund, The Scripps Research Institute
The serotonin receptor encoded by Htr7 (5-hydroxytryptamine (serotonin) receptor 7) mediates the 5-HT-induced phase resetting of the circadian clock within the suprachiasmatic nucleus. It regulates smooth muscle relaxation, is implicated in endocrine regulation and neuropsychiatric disorders and is known to interact with some antidepressant drugs. These mice carry a targeted mutation of the Htr7 gene in which exon 2 is replaced by a NEO cassette. Mice that are homozygous for the targeted mutation are viable and fertile. Although mutant transcript is detected by Northern blot analysis, the many stop codons introduced in the mutant allele should preclude production of a functional protein. Homozygotes exhibit impaired contextual fear conditioning, hippocampus-associated spatial memory, and long term potentiation. In addition to displaying reduced novel location exploration, homozygous mice have shorter and fewer REM sleep episodes. Homozygotes exhibit anti-depressant like behavior as indicated by reduced immobility in forced swim and tail suspension tests and fewer marbles buried in the anxiety and obsessive-compulsive disorder behavioral model test.
A targeting vector designed by Drs. P. B. Hedlund and J. G. Sutcliffe (The Scripps Research Institute) containing a NEO casstte was used to disrupt exon 2. The construct was electroporated into unspecified 129Sv/Ev-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice and then backcrossed to C57BL/6 for 16 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, J Gregor Sutcliffe|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Htr7, 5-hydroxytryptamine (serotonin) receptor 7|
|Strain of Origin||129/Sv|
|Molecular Note||The gene was disrupted by insertion of a neomycin resistance gene into exon 2 via homologous recombination. Northern blot analysis detected mutant transcripts in homozygous mutant animals. It is believed that no functional product is encoded by the mutant transcript due to multiple stop codons within the sequence.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the 5-HT7- mouse strain in a publication, please cite the originating article(s) and include JAX stock #019453 in your Materials and Methods section.