HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/2/R491    most recent 00452.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by D'Andrea, M. R. Articles by Saban, R. Search for Related Content PubMed PubMed Citation Articles by D'Andrea, M. R. Articles by Saban, R.

GENETICALLY MODIFIED ANIMALS AND MODEL ORGANISMS

Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves

¹Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, Spring House, Pennsylvania; ²Department of Physiology, The Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma; ³Pulmonary Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; ⁴Ina Sue Pelmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, Massachusetts; and ⁵Department of Pediatrics, The Children's Hospital at Montefiore and Albert Einstein College of Medicine, Bronx, New York

Submitted 8 July 2004 ; accepted in final form 24 September 2004

A spatial association between mast cells and nerves has been described in both the gastrointestinal and genitourinary tracts. However, the factors that influence the anatomic relationship between mast cells and nerves have not been completely defined. It has been suggested that the high-affinity receptor for substance P [neurokinin-1 (NK₁)] might modulate this interaction. We therefore assessed mast cell-nerve relationships in tissues isolated from wild-type and NK₁ receptor knockout (NK₁^–/–) mice. We now report that, in the complete absence of NK₁ receptor expression, there is a significant increase in the number of mast cells without a change in the anatomic relationship between mast cell and nerves in stomach and bladder tissues at the light microscopic level. We next determined whether transplanted mast cells would maintain their spatial distribution, number, and contact with nerve elements. For this purpose, mast cell-deficient Kit^W/Kit^W–v mice were reconstituted with wild-type or NK₁^–/– bone marrow. No differences in mast cell-nerve contact were observed. These results suggest that NK₁ receptor expression is important in the regulation of the number of mast cells but is not important in the interaction between mast cells and nerves. Furthermore, the interaction between mast cells and nerves is not mediated through NK₁ receptor expression on the mast cell. Further studies are needed to determine the molecular pathway involved in mast cell migration and interaction with nerve elements, but the model of reconstitution of Kit^W/Kit^W–v mice with mast cells derived from different genetically engineered mice is a useful approach to further explore these mechanisms.

cystitis; substance P; disease animal model