A rodent comprising in its genome a genetically modified endogenous Ttr locus comprising a human TTR sequence comprising both TTR coding sequence and non-coding sequence, wherein the genetically modified endogenous Ttr locus comprises an endogenous Ttr promoter, wherein the human TTR sequence is operably linked to the endogenous Ttr promoter, wherein the genetically modified endogenous Ttr locus comprises a human TTR 3' untranslated region, wherein the endogenous Ttr 5' untranslated region has not been deleted and replaced with the corresponding human TTR sequence, and wherein: the entire Ttr coding sequence of the endogenous Ttr locus has been deleted and replaced with the corresponding human TTR sequence, and the region of the endogenous Ttr locus from the Ttr start codon to the Ttr stop codon has been deleted and replaced with the corresponding human TTR sequence; or the genetically modified endogenous Ttr locus encodes a transthyretin precursor protein comprising a signal peptide, the region of the endogenous Ttr locus encoding the signal peptide has not been deleted and replaced with the corresponding human TTR sequence, the first exon of the endogenous Ttr locus has not been deleted and replaced with the corresponding human TTR sequence, and the region of the endogenous Ttr locus from the start of the second Ttr exon to the Ttr stop codon has been deleted and replaced with the corresponding human TTR sequence. wherein the genetically modified endogenous Ttr locus comprises an endogenous Ttr promoter, wherein the human TTR sequence is operably linked to the endogenous Ttr promoter, wherein the genetically modified endogenous Ttr locus comprises a human TTR 3' untranslated region, wherein the endogenous Ttr 5' untranslated region has not been deleted and replaced with the corresponding human TTR sequence, and wherein: the entire Ttr coding sequence of the endogenous Ttr locus has been deleted and replaced with the corresponding human TTR sequence, and the region of the endogenous Ttr locus from the Ttr start codon to the Ttr stop codon has been deleted and replaced with the corresponding human TTR sequence; or the genetically modified endogenous Ttr locus encodes a transthyretin precursor protein comprising a signal peptide, the region of the endogenous Ttr locus encoding the signal peptide has not been deleted and replaced with the corresponding human TTR sequence, the first exon of the endogenous Ttr locus has not been deleted and replaced with the corresponding human TTR sequence, and the region of the endogenous Ttr locus from the start of the second Ttr exon to the Ttr stop codon has been deleted and replaced with the corresponding human TTR sequence. the entire Ttr coding sequence of the endogenous Ttr locus has been deleted and replaced with the corresponding human TTR sequence, and the region of the endogenous Ttr locus from the Ttr start codon to the Ttr stop codon has been deleted and replaced with the corresponding human TTR sequence; or the genetically modified endogenous Ttr locus encodes a transthyretin precursor protein comprising a signal peptide, the region of the endogenous Ttr locus encoding the signal peptide has not been deleted and replaced with the corresponding human TTR sequence, the first exon of the endogenous Ttr locus has not been deleted and replaced with the corresponding human TTR sequence, and the region of the endogenous Ttr locus from the start of the second Ttr exon to the Ttr stop codon has been deleted and replaced with the corresponding human TTR sequence.