A point mutation within CD45 exon A is the cause of variant CD45RA splicing in humans.

Zilch, C; Walker, A; Timón, M; Goff, L; Wallace, D; Beverley, P

Journal article

A point mutation within CD45 exon A is the cause of variant CD45RA splicing in humans.

Abstract:: The leukocyte common antigen (CD45) is alternatively spliced, generating various isoforms expressed on hemopoietic cells. The splicing pattern of CD45 in T cells is altered in some individuals who show abnormal expression of high molecular weight isoforms containing exon A. The variant splicing pattern was shown to be associated with heterozygosity for a silent point mutation within CD45 exon A. This C to G transition is located 77 nucleotides downstream of the splice acceptor junction of exon A (198 bp total length). Here we report that this mutation is the cause of abnormal splicing. To isolate the mutant gene, somatic cell hybrids of lymphocytes with a CD45 splicing defect and a mouse lymphoid line were produced and clones expressing different isoforms of CD45 were isolated. Expression of the high molecular weight isoform containing exon A was associated with the mutation within exon A. All hybrids expressing the low molecular weight isoforms lacking exon A contained the normal allele of CD45 only. In addition, minigenes including this mutation were constructed and transfected into various cell lines (COS-7, HeLa, CHO). Semi-quantitative reverse transcription polymerase chain reaction showed an increase of more than tenfold in splicing to CD45RA (concomitant with a decrease in splicing to CD45RO) when compared with the normal minigene. Taken together, these results demonstrate a causal relationship between the mutation in CD45 exon A and the variant splicing pattern observed. The involvement of trans-acting splicing factors that interact with this region of CD45 pre-mRNA is currently under investigation.

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APA Style

Zilch, C., Walker, A., Timón, M., Goff, L., Wallace, D., & Beverley, P. (1998). A point mutation within CD45 exon A is the cause of variant CD45RA splicing in humans. European Journal of Immunology, 28(1), 22–29.

MLA Style

Zilch, C., et al. “A Point Mutation within CD45 Exon A Is the Cause of Variant CD45RA Splicing in Humans.” European Journal of Immunology, vol. 28, no. 1, 1998, pp. 22–29.

Chicago Style

Zilch, C, A Walker, M Timón, L Goff, D Wallace, and P Beverley. 1998. “A Point Mutation within CD45 Exon A Is the Cause of Variant CD45RA Splicing in Humans.” European Journal of Immunology 28 (1): 22–29.
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