THE RANDOM INACTIVATION OF THE X-CHROMOSOME CARRYING THE DEFECTIVE GENE RESPONSIBLE FOR X-LINKED HYPER IGM SYNDROME (X-HIM) IN FEMALE CARRIERS OF HIGM1
THE RANDOM INACTIVATION OF THE X-CHROMOSOME CARRYING THE DEFECTIVE GENE RESPONSIBLE FOR X-LINKED HYPER IGM SYNDROME (X-HIM) IN FEMALE CARRIERS OF HIGM1
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DOI：
10.1172/jci117377
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发表时间：
1994-08-01
影响因子：
15.9
通讯作者：
ARUFFO, A
中科院分区：
文献类型：
--
作者：
HOLLENBAUGH, D;WU, LH;ARUFFO, A
X连锁高IgM综合征的分子起源最近被确定为CD 40配体gp 39的缺陷，gp 39是活化T细胞表面表达的蛋白质。三个家庭的详细谱系的可用性与受影响的男性允许评估的随机或非随机性质的失活缺陷X染色体以及确定的起源突变。研究X染色体失活是因为与检测HTGM 1携带者的能力和携带者中表型效应的可能性相关。使用免疫染色，PCR和DNA测序，我们发现，gp 39的缺陷基因没有选择性失活。即使在存在非常歪斜的失活，血清IG的正常水平仅仅found. In运营商，其中有缺陷的基因主要是表达，单独染色显示载体状态可靠，而克隆和测序的cDNA是必要的，当正常的基因主要是表达。与其他一些X连锁缺陷不同，极端的Lyonization可能会导致疾病，表达野生型gp 39的少量细胞足以维持正常的体液免疫并预防X-HIM的临床症状。
The molecular origin of X-linked hyper IgM syndrome has recently been identified as a defect in the ligand of CD40, gp39, a protein expressed on the surface of activated T cells. The availability of detailed pedigrees for three families with affected males allowed assessment of the random or nonrandom nature of the inactivation of the defective X chromosome as well as a determination of the origin of the mutation. X chromosome inactivation was studied because of the relevance to the ability to detect carriers of HTGM1 and the potential for phenotypic effect in the carriers. Using immunostaining, PCR, and DNA sequencing, we found that the defective gene for gp39 is not selectively inactivated. Even in the presence of extremely skewed inactivation, normal levels of serum Ig mere found. In carriers in which the defective gene is predominantly expressed, staining alone revealed the carrier status reliably while cloning and sequencing of the cDNA was necessary when the normal gene was predominantly expressed. Unlike some other X-linked defects where extreme Lyonization may lead to disease, a small population of cells expressing the wild-type gp39 is sufficient to maintain normal humoral immunity and prevent the clinical symptoms of X-HIM.