New insights into the melanophilin (MLPH) gene controlling coat color phenotypes in American mink

Abstract

The mutation causing the Silverblue color type (pp) is one of the most used recessive mutations within American mink (Neovison vison) fur farming, since it is involved in some of the popular color types such as Violet and Saphire which originate from a combination of recessive mutations. In the present study, the genomic and mRNA sequences of the melanophilin (MLPH) gene were studied in Violet, Silverblue and wild-type (wt) mink animals. Although breeding schemes and previous literature indicates that the Violet (aammpp) phenotype is a triple recessive color type involving the same locus as the Silverblue (pp) color type, our findings indicate different genotypes at the MLPH locus. Upon comparison at genomic level, we identified two deletions of the entire intron 7 and of the 5' end of intron 8 in the sequence of the Silverblue MLPH gene. When investigating the mRNA, the Silverblue animals completely lack exon 8, which encodes 65 residues, of which 47 define the Myosin Va (MYO5A) binding domain. This may cause the incorrect anchoring of the MLPH protein to MYO5A in Silverblue animals, resulting in an improper pigmentation as seen in diluted phenotypes. Additionally, in the MLPH mRNA of wt, Violet and Silverblue phenotypes, part of intron 8 is retained resulting in a truncated MLPH protein, which is 359 residues long in wt and Violet and 284 residues long in Silverblue. Subsequently, our findings point out that the missing actin-binding domain, in neither of the 3 analyzed phenotypes affects the transport of melanosomes or the consequent final pigmentation. Moreover, the loss of the major part of the MYO5A domain in the Silverblue MLPH protein seems to be the responsible for the dilute phenotype. Based on our genomic DNA data, genetic tests for selecting Silverblue and Violet carrier animals can be performed in American mink.

Interactions of allele E of the MC1R gene with FM and mutations in the MLPH gene cause the five-gray phenotype in the Anyi tile-like gray chicken

“…Studies have shown that the protein complexes encoded by MLPH, RAB27A, and MYO5A are required for melanosome transport (Ménasché et al, 2003). In several species, such as humans, cats, dogs, horse, mink, rabbit, and quail, defects in MYO5A, RAB27A, and MLPH were found to cause a phenotypically identical pigmentary dilution (Wilson et al, 2000;Matesic et al, 2001;Ménasché et al, 2000Ménasché et al, , 2003Philipp et al, 2005;Ishida et al, 2006;Bed'hom et al, 2012;Cirera et al, 2013;Fontanesi et al, 2014). Results of the association analysis showed that only one SNP in MLPH was significantly associated with the gray plumage color phenotype, suggesting that the MLPH gene might be closely associated with the gray plumage color phenotype.…”

“…Studies in chicken and quail showed that the lavender plumage color dilution phenotype was caused by a mutation in the MLPH gene (Vaez et al, 2008;Bed'hom et al, 2012), and that the protein complexes encoded by MLPH, RAB27A, and MYO5A were required for melanosome transport. In fact, mutations in MLPH, RAB27A, and MYO5A can all lead to the dilution phenotype in animals (Matesic et al, 2001;Ménasché et al, 2003;Philipp et al, 2005;Ishida et al, 2006;Bed'hom et al, 2012;Cirera et al, 2013;Fontanesi et al, 2014). Presumably, the "gray" phenotype is derived from the black phenotype (i.e., black feathers, shanks, skin, beak, and comb).…”

Variation in pigmentation gene expression is associated with distinct aposematic color morphs in the poison frog, Dendrobates auratus

“…The product of the melanophilin gene forms a 307 complex that combines with two other proteins and binds melanosomes to the cell cytoskeleton, facilitating 308 melanosome transport within the cell. Variants of this gene are associated with "diluted", or lighter-colored, 309 melanism in a number of vertebrates (Cirera et al 2013). Similarly, the mreg (melanoregulin) gene product functions 310 in melanosome transport and hence is intimately involved in pigmentation (Wu et al 2012).…”

“…Similarly, the airc gene plays a critical role in guanine synthesis, and yeast with mutations in this 332 gene leading to aberrant forms of the transcribed protein are unable to synthesize adenine and accumulate a visible 333 red pigment (Tolstorukov and Efremov 1984;Sychrova et al 1999). Similarly, the mthfd (methylenetetrahydrofolate 334 dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1) gene also affects the de novo purine 335 synthesis pathway (Christensen et al 2013). The genes airc, gart, and mthfd had similar expression patterns and 336 were very lowly expressed in the mostly green microspot population.…”

A frameshift mutation in the melanophilin gene causes the dilute coat colour in rabbit (Oryctolagus cuniculus) breeds

“…) and American mink (Cirera et al . ). In chicken and Japanese quail, MLPH mutations are responsible for the lavender plumage colour (Vaez et al .…”