Basic-alimentary tractThe ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function
Section snippets
Generation of ASIC1−/− mice
Mice with a disrupted ASIC1 gene were generated by homologous recombination in embryonic stem cells as we have described previously.13 In the targeted allele, a phosphoglycerate kinase (PGK)-neo cassette replaces the first exon of the ASIC1 gene and approximately 400 bp of upstream sequence. Heterozygote pairs of mice were mated to generate animals for the current investigation. Homozygous ASIC1+/+ or −/− littermates were selected blindly for experiments after genotyping and results were
ASIC1 is expressed in sensory neurons
By using RT-PCR analysis, we detected both ASIC1 splice variants (ASIC1a and ASIC1b) in the nodose ganglion (where cell bodies of vagal afferents are located) of +/+ mice (Figure 2A). It previously has been shown that ASIC1 also is expressed in DRG sensory neurons,25 which innervate the skin and colon. Consistent with those data, we found ASIC1a and 1b transcripts in DRG by RT-PCR (Figure 2A). In ASIC1−/− mice, ASIC1a transcripts were eliminated, although RT-PCR still could detect a signal for
Discussion
One of the key aims of current neurobiology is to identify a means of selectively modulating sensory input to the central nervous system. Thus, it is important to define mechanosensory mechanisms in specific populations of sensory neurons that supply different regions of the body. The gut relies on a wealth of mechanosensory input to maintain normal function. Thus, identifying the molecules that influence visceral mechanosensation may lead to an improved understanding of gastrointestinal
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Cited by (0)
Supported by the National Health and Medical Research Council of Australia, Deutsche Forschungsgemeinshaft, and the Howard Hughes Medical Institute.
- 1
Carlos Martinez-Salgado is currently with the Unidad de Investigación, Hospital Universitario de Salamanca, Spain.
- 2
A.J.P., S.M.B., and C.M.M. contributed equally to this work.