Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient Kit(W-sh)/Kit(W-sh) sash mice.
BACKGROUND
Mast cell-deficient Kit(W)/Kit(W-v) mice are an important resource for studying mast cell functions in vivo. However, because they are compound heterozygotes in a mixed genetic background and are infertile, they cannot be crossed easily with other mice.


OBJECTIVE
To overcome this limitation, we explored the use of Kit(W-sh)/Kit(W-sh) mice for studying mast cell biology in vivo.


RESULTS
These mice are in a C57BL/6 background, are fertile and can be bred directly with other genetically modified mice. Ten-week-old Kit(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 of Kit(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 10(7) bone marrow-derived mast cells (BMMC) into tail veins of Kit(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 splenectomized Kit(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.


CONCLUSIONS
In summary, these findings show that mast cell-deficient Kit(W-sh)/Kit(W-sh) mice possess unique attributes that favour their use for studying mast cell functions in vivo.
Wolters
P J
PJ
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0911, USA. pjwolt@itsa.ucsf.edu
Mallen-St Clair
J
J
Lewis
C C
CC
Villalta
S A
SA
Baluk
P
P
Erle
D J
DJ
Caughey
G H
GH
D000818:Animals; D017353:Gene Deletion; D020869:Gene Expression Profiling; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D008407:Mast Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D013154:Spleen / Q000276:immunology
D019009:Proto-Oncogene Proteins c-kit