Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice.
The mouse lpr (lymphoproliferation) mutation carries a rearrangement in the chromosomal gene for the Fas antigen, which mediates apoptosis. Isolation and characterization of mouse Fas antigen chromosomal gene from wild-type and lpr mice indicated an insertion of an early transposable element (ETn) in intron 2 of the Fas antigen gene of lpr mice. Hybrid transcripts carrying the Fas antigen and ETn sequences were expressed in the thymus and liver of the mutant. This indicated that premature termination and aberrant splicing of the Fas antigen transcript caused by the insertion of the ETn in the intron are responsible for the lymphoproliferation and autoimmune phenotype of the mutant mouse. On the other hand, an insertion of the ETn into an intron of a mammalian expression vector dramatically but not completely reduced the expression efficiency. These findings suggest that lpr mice are able to express a very low level of the Fas antigen.
Adachi
M
M
Osaka Bioscience Institute, Japan.
Watanabe-Fukunaga
R
R
Nagata
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D017209:Apoptosis; D001483:Base Sequence; D004251:DNA Transposable Elements; D005786:Gene Expression Regulation; D007438:Introns; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D014158:Transcription, Genetic; D019014:fas Receptor
D000954:Antigens, Surface; D004251:DNA Transposable Elements; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D019014:fas Receptor