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. 2019 Nov 15;12(11):dmm041103. doi: 10.1242/dmm.041103

Fig. 2.

Fig. 2.

TTN is the nsh gene. (A) Genetic mapping of the nsh locus on the medaka linkage group 21 (LG 21). To define the nsh gene, we scored 2016 fish from nsh/+×nsh/+ mapping crosses. Single-strand conformation polymorphism markers from intron 193-194 and the 3′UTR of TTN confined nsh to a 19.0-kb critical region. (B) DNA sequence analysis of cDNAs from the nsh and WT strains revealed an adenine-to-thymine mutation in nsh, causing D (aspartic acid)-23186 to V (valine) mutation (red arrow), located in exon 204. (C) Modular structure of the M-line–A-band transition zone of titin contains a binding site for muscle-specific ring finger protein 1 (MURF1). The missense mutation identified in nsh was located in an Ig domain near this site. (D) Clustal W alignment of human, mouse, zebrafish and medaka TTN sequences. Medaka titin and human titin proteins share 62% similarity. GenBank or Ensembl accession numbers used for the analysis are as follows: human TTN (NM_133378), mouse Ttn (NP_035782), zebrafish ttna (DQ649453) and medaka TTN (ENSORLT00000022736). Alignment of titin protein from several species along with the nsh mutation showed that the mutation affected the evolutionary conserved amino acid residue (red asterisk). Identical and similar amino acids are indicated by dark blue and light blue boxes, respectively.