Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficientKit W-sh/ Kit W-sh sash mice.

Mast cell-deficientKit ^W/ Kit ^W-v mice are an important resource for studying mast cell functionsin vivo. However, because they are compound heterozygotes in a mixed genetic background and are infertile, they cannot be crossed easily with other mice.To overcome this limitation, we explored the use ofKit ^W-sh/ Kit ^W-sh mice for studying mast cell biologyin vivo.These mice are in a C57BL/6 background, are fertile and can be bred directly with other genetically modified mice. Ten-week-oldKit ^W-sh/ Kit ^W-sh are profoundly mast cell-deficient. No mast cells are detected in any major organ, including the lung. Gene microarrays detect differential expression of just seven of 16 463 genes in lungs ofKit ^W-sh/ Kit ^W-sh mice compared with wild-type mice, indicating that resting mast cells regulate expression of a small set of genes in the normal lung. Injecting 10⁷ bone marrow-derived mast cells (BMMC) into tail veins ofKit ^W-sh/ Kit ^W-sh mice reconstitutes mast cell populations in lung, stomach, liver, inguinal lymph nodes, and spleen, but not in the tongue, trachea or skin. Injection of BMMC into ear dermis or peritoneum reconstitutes mast cells locally in these tissues. When splenectomizedKit ^W-sh/ Kit ^W-sh mice are intravenously injected with BMMC, mast cells circulate longer and are found more often in the liver and inguinal lymph nodes, indicating that the spleen acts as a reservoir for mast cells following injection and limits migration to some tissues.In summary, these findings show that mast cell-deficientKit ^W-sh/ Kit ^W-sh mice possess unique attributes that favour their use for studying mast cell functionsin vivo. [ABSTRACT FROM AUTHOR]