Mouse Hair Significantly Lightened Through Replacement of the Cysteine Residue in the N-Terminal Domain of Mc1r Using the CRISPR/Cas9 System
| Autor: | Hitoshi Suzuki, Gohta Kinoshita, Kimi Araki, Koki Noju, Takeru Tsunoi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
0301 basic medicine Coat Population Mutant Biology medicine.disease_cause 010603 evolutionary biology 01 natural sciences Frameshift mutation 03 medical and health sciences Mice melanocortin 1 receptor Loss of Function Mutation Genetics medicine Animals Cysteine education Hair Color Molecular Biology Gene CRISPR/Cas9 Genetics (clinical) Gene Editing Mice Knockout Mutation education.field_of_study Molecular biology 030104 developmental biology Phenotype hair color variant loss of function Receptor Melanocortin Type 1 Biotechnology Melanocortin 1 receptor |
| Zdroj: | Journal of Heredity. 111(7):640-645 |
| ISSN: | 0022-1503 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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