Shubitowski D M, Wills-Karp M, Ewart S L
Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA.
Cytogenet Genome Res. 2002;97(1-2):133-5. doi: 10.1159/000064054.
Complement factor 5a (C5a) promotes local inflammation and is a potent chemoattractant for neutrophils and macrophages. We had an interest in C5a and its receptor, C5r1, because we previously identified C5a as a positional candidate gene for the quantitative trait locus Abhr2, which determines allergen-induced bronchial hyperresponsiveness in our murine model of asthma. To study the significance of C5r1 in our asthma model we first had to determine its genomic map location in mice. Genomic sequence surrounding murine C5r1 was analyzed for polymorphisms and two variable microsatellites were identified. These microsatellites were genotyped in A/J x (C3H/HeJ x A/J)F1 backcross mice (n = 355) and mapped in a panel of 164 markers spaced at approximately 10 cM intervals throughout the genome. Multipoint linkage analysis placed C5r1 on murine chromosome 7, 3.9 cM from the top of the linkage group. This map location has been previously identified as containing an additional quantitative trait locus for allergen-induced airway hyperresponsiveness, Abhr3, in this population of mice.
补体因子5a(C5a)可促进局部炎症,是中性粒细胞和巨噬细胞的强效趋化因子。我们对C5a及其受体C5r1感兴趣,因为我们之前将C5a鉴定为数量性状基因座Abhr2的位置候选基因,该基因座决定了我们哮喘小鼠模型中变应原诱导的支气管高反应性。为了研究C5r1在我们的哮喘模型中的意义,我们首先必须确定其在小鼠中的基因组图谱位置。分析了小鼠C5r1周围的基因组序列的多态性,并鉴定了两个可变微卫星。这些微卫星在A/J×(C3H/HeJ×A/J)F1回交小鼠(n = 355)中进行基因分型,并在全基因组中以约10 cM间隔分布的164个标记物的面板中进行定位。多点连锁分析将C5r1定位在小鼠7号染色体上,距连锁群顶部3.9 cM。该图谱位置先前已被确定为在该小鼠群体中包含变应原诱导的气道高反应性的另一个数量性状基因座Abhr3。