THE MURINE MUTATION JAUNDICED IS CAUSED BY REPLACEMENT OF AN ARGININEWITH A STOP CODON IN THE MESSENGER-RNA ENCODING THE 9TH REPEAT OF BETA-SPECTRIN

The jaundiced, ja/ja, mouse mutant has a severe hemolytic anemia assoc iated with a deficiency of beta-spectrin in erythrocyte ghosts. Genes for the disease phenotype and beta-spectrin colocalize on Chromosome 1 2. beta-Spectrin mRNA is not detected in reticulocytes or in brain fro m newborn mutant mice. To locate the nucleotide sequence alteration, t he erythroid beta-spectrin transcript from mutant spleen was amplified by reverse transcription PCR and sequenced. A C-to-T alteration is pr esent in the mutant transcript and produces a premature stop codon fro m an arginine codon in mRNA encoding repeat 9 of beta-spectrin at amin o 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 strain s, 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 mRN A of jaundiced mice.