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. 2009 Oct;8(7):699–713. doi: 10.1111/j.1601-183X.2009.00514.x

Figure 1:

Figure 1:

(a) Haplotypes of backcross and intercross progeny segregating the Cloth-ears mutation. The Cloth-ears (Clth) mutation arose on a mutagenized (BALB/cAnN × C3H/HeH)F1 individual. Sixty-four backcross progeny with a reduced startle response and/or an intermittent tremor and 26 intercross progeny with or without a continuous tremor were mapped across chromosome 8 and genotyped at recombinant markers. The genetic data indicates that the mutagenized chromosome was from the BALB/cAnN strain. The Cloth-ears mutation is non-recombinant with the SNP markers Scn8a_SNP and rs4231023 and maps to the interval D15Mit97.2–rs8266857. (b) Chromatograms of the Cloth-ears mutation from wild-type (+/+) and Scn8aClth/Scn8aClth DNA. Arrow: base 2942 of the Scn8a coding sequence, showing an adenine (A) in wild-type mice and a thymine (T) in Scn8aClth/Scn8aClth mice (arrow). The predicted amino acid sequence from wild-type and Scn8aClth/Scn8aClth mice is also indicated, highlighting the D981V change. (c) Position of the Cloth-ears mutation (D981V) in the SCN8A amino acid sequence. D981V resides within the predicted domain 2 (D2) of the SCN8A peptide, six amino acids downstream of the S6 transmembrane segment. The amino acid sequence of domain 2 (D2) is shown in black; sequence of domain 2 segment 6 (D2S6) is shown in pink and the position of the Cloth-ears mutation (D981V) is shown in bold red. (d) Schematic of the voltage-gated sodium channel α- and β-subunit proteins (adapted from Meisler & Kearney 2005). The α-subunit comprises four homologous domains (D1–D4 or DI–DIV), which are shown in different colours, each containing six transmembrane segments (S1–S6). S4 segments function as voltage sensors and the S5–S6 loops form the outer pore. A pore structure is formed by the transmembrane segments in the membrane (inset). The location of the Cloth-ears mutation is shown (red star). (e) Alignment of peptide sequences of SCN8A orthologues and other mouse SCN α-subunits (Ensembl) in the region of amino acid 981 (arrow). Alignments were made using clustal-W web-based software.