Tg(TTR-V30M)14Imeg

The transgene comprises a 7.6-kilobase genomic DNA fragment containing the entire human transthyretin gene, with a mutation causing substitution of methionine for valine at amino acid position 30, and approximately 0.6 kb of upstream sequence isolated from a patient with familial amyloidotic polyneuropathy. Southern blot analysis showed that five to six copies had integrated tandemly. Human transthyretin mRNA was expressed in liver and yolk sac and was detected in serum, but not in several other tissues examined, including brain. However, the human transcript is expressed ectopically in the head, excluding the brain, of line 14 fetuses at gestational days (E) 10.5 through E15, but not at E9.5. (Transgenic lines not exhibiting the craniofacial phenotype did not express TTR mRNA in head at E10.5.) Human transthyretin was found to associate with the endogenous mouse protein to form chimeric tetramers. (J:92524)