open access

https://hdl.handle.net/2115/82865

Mouse Hair Significantly Lightened Through Replacement of the Cysteine Residue in the N-Terminal Domain of Mc1r Using the CRISPR/Cas9 System

英語

melanocortin 1 receptor

2020-10

Oxford University Press

Journal of Heredity

111(7)

640-645

A loss-of-function mutation in the melanocortin 1 receptor gene (MC1R), which switches off the eumelanin production, causes yellowish coat color variants in mammals. In a wild population of sables (Martes zibellina) in Hokkaido, Japan, the mutation responsible for a bright yellow coat color variant was inferred to be a cysteine replacement at codon 35 of the N-terminal extracellular domain of the Mc1r receptor. In the present study, we validated these findings by applying genome editing on Mc1r in mouse strains C3H/HeJ and C57BL/6N, altering the codon for cysteine (Cys33Phe). The resulting single amino acid substitution (Cys33Phe) and unintentionally generated frameshift mutations yielded a color variant exhibiting substantially brighter body color, indicating that the Cys35 replacement produced sufficient MC1R loss of function to confirm that this mutation is responsible for producing the Hokkaido sable yellow color variant. Notably, the yellowish mutant mouse phenotype exhibited brown coloration in subapical hair on the dorsal side in both the C3H/HeJ and C57BL/6N strains, despite the inability of the latter to produce the agouti signaling protein (Asip). This darker hair and body coloration was not apparent in the Hokkaido sable variant, implying the presence of an additional genetic system shaping yellowish hair variability.

学術雑誌論文

Accepted Manuscript

This is a pre-copyedited, author-produced version of an article accepted for publication in "Journal of Heredity" following peer review. The version of record "Journal of Heredity. 111(7), 2020, p.640–645" is available online at: https://doi.org/10.1093/jhered/esaa054

0022-1503

AA00699204