The murine mutation jaundiced is caused by replacement of an arginine with a stop codon in the mRNA encoding the ninth repeat of beta-spectrin.
The jaundiced, ja/ja, mouse mutant has a severe hemolytic anemia associated with a deficiency of beta-spectrin in erythrocyte ghosts. Genes for the disease phenotype and beta-spectrin colocalize on Chromosome 12. beta-Spectrin mRNA is not detected in reticulocytes or in brain from newborn mutant mice. To locate the nucleotide sequence alteration, the erythroid beta-spectrin transcript from mutant spleen was amplified by reverse transcription PCR and sequenced. A C-to-T alteration is present in the mutant transcript and produces a premature stop codon from an arginine codon in mRNA encoding repeat 9 of beta-spectrin at amino acid position 1160. The point mutation introduces a Dde I site that is present in PCR-amplified DNA of ja/ja and ja/+ mice but not of +/+ control mice from the strain of origin, 129/Sv, or from the two strains, WB/Re and C57BL/6J, in which the mutation has been fixed by over 53 generations of backcrossing. The genetic data confirm that the point mutation is responsible for the severe reductions in beta-spectrin mRNA of jaundiced mice.
Bloom
M L
ML
Jackson Laboratory, Bar Harbor, ME 04609.
Kaysser
T M
TM
Birkenmeier
C S
CS
Barker
J E
JE
D000595:Amino Acid Sequence; D000743:Anemia, Hemolytic / Q000097:blood / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003062:Codon; D003433:Crosses, Genetic; D017931:DNA Primers; D006579:Heterozygote; D006720:Homozygote; D007565:Jaundice / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D012091:Repetitive Sequences, Nucleic Acid; D012156:Reticulocytes / Q000378:metabolism*; D013049:Spectrin / Q000235:genetics*; D014158:Transcription, Genetic
D003062:Codon; D017931:DNA Primers; D012333:RNA, Messenger; D013049:Spectrin; D001120:Arginine