C-Kit mutant mice have a selective loss of vagal intramuscular mechanoreceptors in the forestomach

Intramuscular arrays are one of two major classes of vagal afferent mechano receptors that innervate the smooth muscle wall of the proximal gastrointes tinal tract. They consist of rectilinear telodendria that distribute in the muscle sheets, parallel to the long axes of muscle fibers. Intramuscular a rrays appear to make direct contact with the muscle fibers, but they also c ourse on, and form appositions with, intramuscular interstitial cells of Ca jal. These complexes formed by intramuscular arrays and intramuscular inter stitial cells of Cajal suggest that intramuscular arrays might require eith er structural or trophic support of the interstitial cells of Cajal for nor mal differentiation and/or maintenance. To evaluate this hypothesis, we hav e examined the morphology and distribution of vagal afferent endings in the c-Kit mutant mouse that lacks intramuscular interstitial cells of Cajal. V agal afferents were labeled by nodose ganglion injection of either wheat ge rm agglutinin-horseradish peroxidase conjugate or a tagged dextran, and the labeled afferent terminals in the stomach were mapped using a standardized quantitative sampling scheme. Intramuscular arrays were dramatically reduc ed (in circular muscle by 63%; in longitudinal muscle by 78%) in the c-Kit mutant mice relative to their wild-type littermates. Additionally, a substa ntial number of the surviving axons and terminals in the mutant stomachs we re morphologically aberrant. Moreover, the loss of intramuscular arrays in mutants appeared to be selective: the structure, distribution and density o f intraganglionic laminar endings, i.e., the other vagal mechanoreceptors i n smooth muscle, were not significantly altered. Finally, the conspicuous d ecrease in intramuscular array density in mutants was associated with a non -significant trend toward loss of nodose ganglion neurons. Collectively the se findings suggest that interstitial cells are required for the normal dev elopment or maintenance of vagal intramuscular arrays. Therefore, the c-Kit mutant mouse will be valuable for determining the role(s) of interstitial cells in intramuscular array development as well as for providing an animal model with the intramuscular array class of vagal afferents selectively ab lated.