Structure of the mouse CD72 (Lyb-2) gene and its alternatively spliced transcripts

Area of Science:

• Immunogenetics
• Molecular Biology
• Genomics

Background:

• The CD72 gene is involved in mammalian immunodifferentiation.
• Allelic variations in CD72 (CD72a, CD72b, CD72c) have been observed.
• Understanding CD72 gene structure and splicing is crucial for studying immune cell development.

Purpose of the Study:

• To report the complete genomic sequence of the CD72 gene from the C57L mouse.
• To investigate the mechanisms of CD72 gene polymorphism, including alternative splicing.
• To analyze allele-specific usage of splice sites and its impact on CD72 mRNA variants.

Main Methods:

• Genomic sequencing of the CD72 gene and its flanking regions.
• Comparative cDNA sequence analysis of CD72 alleles.
• Polymerase Chain Reaction (PCR) analyses to study splice site usage.
• Analysis of CD72 mRNA distribution in mouse splenic B cells.

Main Results:

• The complete CD72 gene sequence spans 6830 base pairs with nine exons and eight introns.
• The CD72 gene features a TATA-less promoter, suggesting regulation during immunodifferentiation.
• Two distinct seven amino acid insertion/deletions were identified among CD72 alleles.
• Alternative splicing, including exon skipping and allele-specific splice site selection (AG sites), generates CD72 mRNA polymorphism.
• Allele-specific distributions of CD72 mRNAs lacking sequences from exon 3 and/or exon 4 were observed in splenic B cells.

Conclusions:

• The CD72 gene structure and its alternative splicing mechanisms contribute significantly to CD72 polymorphism.
• Allele-specific splicing events result in diverse CD72 mRNA variants, potentially influencing immune responses.
• Further research is needed to elucidate the in vivo functions of CD72 protein isoforms generated by alternative splicing.