DKK4 as a novel candidate marker for Zhexi Angora rabbit wool quality

Wool quality is an important economic trait in Angora rabbits, and is influenced by the growth and development of hair follicles (HFs). This study investigates the role of Dickkopf-related protein 4 (DKK4) on the regulation of wool quality. Overexpression and knockdown of DKK4 in dermal papilla cells (DPCs) showed that DKK4 modulated genes associated with HF growth and development, and DKK4 could also inhibit the proliferation of DPCs. Investigation of the relationships between single-nucleotide polymorphisms (SNPs) in DKK4 and wool quality traits (fibre diameters and lengths of fine and coarse wool, coarse wool percentage) identified four SNPs located in the exons of DKK4 in 108 Zhexi Angora rabbits. Of these, C2351T and C2405G conformed to the Hardy-Weinberg equilibrium and two identified haplotypes showed linkage disequilibrium. Analysis of correlations between the three haplotype combinations and wool quality showed that the mutant haplotype combination TT/GG was associated with significantly higher fibre diameters of fine wool compared with the CC/CC and CT/CG haplotype combinations. Bioinformatics analysis showed that DKK4 encoded a 222-amino acid protein that was both unstable and hydrophilic. The non-synonymous C2351T and C2405G mutations had no effect on the DKK4 protein structure. In conclusion, the findings provide a theoretical basis for using DKK4 as a potential molecular marker for the selection of wool fibre diameter traits in Angora rabbits.