CD72几种新的剪切形式的发现及它们在红斑狼疮模型鼠中的差异表达

Identification of Eight Novel Alternative Splicing Forms of CD72 and Their Differential Expression in a Mouse Model of SLE

CD72是一个重要的B细胞特异性受体,它以多种选择性剪切形式存在.在小鼠脾细胞中发现并鉴定了8种新的CD72选择性剪切形式,这些剪切形式中包含有2种独特的插入片段,一种选择性剪切保留了一个内含子(intron1),而这个内含子被翻译成氨基酸序列后并没有改变前后外显子的读码框,另一种使用了一个位于内含子之内的3′剪切位点,从而产生移码,提前终止了蛋白质的开放读码框,称为3′AS(3′alternative splicingsite).比较了CD72所有剪切形式在BALB/C小鼠和NZB/W小鼠中的差异表达,发现:a.含有3′AS的剪切形式的表达都很少;b.WT,+In1,+In1-Ex3和-Ex3的表达在BLAB/C小鼠中比在NZB/W小鼠中高;c.没有ITIM2的-Ex2-Ex3剪切形式在NZB/W小鼠中有特异性高表达.这些结果提示,CD72的多种选择性剪切形式在调控B细胞受体信号转导过程中可能发挥着不同的作用,并与系统性红斑狼疮的发病密切相关.

CD72 is a B cell specific receptor that exists in multiple alternative splicing forms. Eight novel alternative splicing forms of CD72 were identified from the spleenocytes of BALB/C mice. Two very unique intron sequences were found in those alternative splicing forms. One kind of splicing variants retained the intronl in the mRNA. This intron can be translated into 32 amino acid residues without changing the reading frame of the whole proteins. Another kind of splicing variants used an alternative 3＇ splice site in intron 3 （3＇AS） which led to premature termination of its encoded protein. The differential expression of the CD72 splicing variants were compared in BALB/C and NZB/W mice that were at different stage of systematic lupus erythematosis （SLE） disease development. It was found that 1） splicing forms containing YAS was rare in all samples examinated; 2） splicing forms containing two ITIM domains and transmembrane domains were more abundant in BALB/C mice than in NZB/W mice, even in some cases the two ITIM domains were separated by the intron 1; 3） a shorter splicing form with both exon2 and exon3 missing was expressed highly in terminally diseased NZB/W mice.These results suggested an important role of CD72 alternative splicing forms in B cell receptor signaling and in SLE.