Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient KitW-sh/KitW-sh sash mice
Tissue-selective mast cell reconstitution and differential lung gene expression in mast cell-deficient KitW-sh/KitW-sh sash mice
复制标题
DOI：
10.1111/j.1365-2222.2005.02136.x
复制
发表时间：
2005-01-01
影响因子：
6.1
通讯作者：
Caughey, GH
中科院分区：
文献类型：
--
作者：
Wolters, PJ;Mallen-St Clair, J;Caughey, GH
背景肥大细胞缺陷型Kit（W）/Kit（W-v）小鼠是研究肥大细胞功能的重要动物模型。目的探讨Kit（W-sh）/Kit（W-sh）小鼠在体内肥大细胞生物学研究中的应用。十周大的Kit（W-sh）/Kit（W-sh）严重缺乏肥大细胞。在包括肺在内的任何主要器官中均未检测到肥大细胞。基因微阵列检测到与野生型小鼠相比，Kit（W-sh）/Kit（W-sh）小鼠肺中16463个基因中仅7个基因的差异表达，表明静息肥大细胞调节正常肺中一小部分基因的表达。将10（7）个骨髓来源的肥大细胞（BMMC）注射到Kit（W-sh）/Kit（W-sh）小鼠的尾静脉中重建肺、胃、肝、腹股沟淋巴结和脾中的肥大细胞群，但不重建舌、气管或皮肤中的肥大细胞群。将BMMC注射到耳真皮或腹膜中可局部重建这些组织中的肥大细胞。当脾切除的Kit（W-sh）/Kit（W-sh）小鼠静脉注射BMMC时，肥大细胞循环时间更长，并且更常见于肝脏和腹股沟淋巴结中，表明脾在注射后充当肥大细胞的储存库，并限制了向某些组织的迁移。这些发现表明肥大细胞缺陷型Kit（W-sh）/Kit（W-sh）小鼠具有有利于它们用于研究体内肥大细胞功能的独特属性。
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.Conclusion 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.