Effect of coat color genes on the hair pigmentation morphology in the american mink (<Emphasis Type="Italic">Mustela vison</Emphasis> Schr. L.)

The morphological patterns of hair pigmentation (the size and shape of pigment granules and their distribution among layers) have been studied in four compound coat color forms of the American mink: moil-sapphire also known as violet (genotype m/m a/a p/p); moil-silver or sage (genotype m/m p/p); the color form determined by genotype m/+ a/a; and platinum leopard (S ^k /+ a/+ p/p). The hair pigmentation pattern specific for each coat color form and its difference from the standard coat color of the American mink (genotype +/+) has been determined. The possible mechanisms of the phenotypic expression of the nonallelic genes contributing to the described compound color forms are discussed.     

Effect of mutations affecting coat color on the blood lymphocyte structure in the American mink (Mustela vison Schreber, 1777)

American minks with different genotypes containing the Aleutian coat color allele in the homozygous state, including the single recessive Aleutian (a/a); double recessive sapphire (a/a p/p) and lavender (m/m a/a); triple recessive violet (m/m a/a p/p); and dominant-recessive cross sapphire (S/+ a/a p/p), sapphire leopard (S(K)/+ a/a p/p), and shadow sapphire (S(H)/+ a/a p/p) minks, as well as American minks without the Aleutian allele, including the standard (+/+); single recessive silver-blue (p/p) and hedlund-white (h/h); double recessive pearl (k/k p/p), Finnish topaz (t(S)/t(S) b/b); incompletely dominant royal silver (S(R)/+), standard leopard (S(K)/+), and black crystal (C(R)/+); and dominant-recessive snowy topaz (C(R)/+ t(S)/t(S) b/b) and Kujtezhy-spotted (S(K)/+ b/b) minks have been studied. Homozygosity for the a allele has been found to disturb the subcellular structure of leukocyte, namely the formation of abnormally large granules.     

Mutant gene expression in mouse aggregation chimeras. 8. The effect of the white gene on coat pigmentation

Aggregation of mouse embryos produced 11 chimaeras Miwh/+C/C----+/+c/c and 8 chimaeras +/+C/C----+/+c/c (control). Chimaerism was detected by mosaicism of coat retinal pigment epithelium and by electrophoretic pattern of glucose phosphate isomerase. All chimaeras showed a common pattern of pigmented and unpigmented hair regions that alternated as stripes of different length and width and extended from spine in lateral-ventral direction. However, white coat color predominated in Miwh/+C/C----+/+c/c chimaeras due to a higher proportion of unpigmented zones as well as to weakening of hair color in pigmented areas. Besides, distal regions of limbs were always unpigmented in Miwh/+C/C----+/+c/c chimaeras and completely or partially pigmented in +/+C/C----+/+c/c chimaeras. Pigmented hair regions are often located on the ventral trunk surface where the Miwh/+ heterozygotes usually had an unpigmented spot. The examination of hairs, taken from the same regions of gray coloration, revealed the presence of pigmented, unpigmented and mosaic hairs. The proportion of unpigmented hairs was much higher in Miwh/+C/C----+/+c/c chimaeras than in +/+C/C----+/+c/c chimaeras. The data obtained indicate that a single Miwh gene dose reduced proliferative activity of melanoblasts which resulted in weakening of coat pigmentation.     

A frameshift mutation in the LYST gene is responsible for the Aleutian color and the associated Chédiak–Higashi syndrome in American mink

One of the colors of mink is Aleutian (aa)—a specific gun‐metal gray pigmentation of the fur—commonly used in combination with other color loci to generate popular colors such as Violet (aammpp) and Sapphire (aapp). The Aleutian color allele is a manifestation of mink Chédiak‐Higashi syndrome (CHS), which has been described in humans and several other species. As with forms of CHS in other species, we report that the mink CHS is linked to the lysosomal trafficking regulator ( LYST ) gene. Furthermore, we have identified a base deletion (c.9468delC) in exon 40 of LYST, which causes a frameshift and virtually terminates the LYST product prematurely (p.Leu3156Phefs*37). We investigated the blood parameters of three wild‐type mink and three CHS mink. No difference in the platelet number between the two groups was observed, but an accumulation of platelets between the groups appears different when collagen is used as a coagulant. Microscopic analysis of peripheral blood indicates giant inclusions in the neutrophils of the Aleutian mink types. Molecular findings at the LYST locus enable the development of genetic tests for analyzing the color selection in American mink.     

Hair growth in mouse mutants affecting coat texture

The genetic control of hair growth has been studied in mice carrying the following coat texture genes: fz (fuzzy), soc (soft coat), hid (hair interior defect), sa (satin), It (lustrous), Ve (velvet), wa-1 (waved-1), Re (rex), Re ^wc (wavy coat) and pk (plucked).
A general effect on cells of epidermal origin, found in soc/soc and Ve /+ skin samples illustrates how common factors control developmental potential in both the stratum germinativum and the follicle bulb. A direct influence on follicle bulb development is also seen in fz/fz homozygotes in which the dermal papilla functions abnormally. The role of the bulb cells and the dermal papilla in the control of hair shaft calibre is discussed.
hid is a new gene, found in homozygous condition in all mice of the AKR inbred strain. hid and sa appear primarily to be concerned in the differentiation of the medulla.
In the hair waving mutants, waved-1, rex and wavy coat, the processes controlling hair movement within the follicle are disturbed. These genes appear to regulate internal root sheath function. When the normal relationship between internal root sheath and developing hair shaft is disturbed, shaft movement slows, with the subsequent development of shaft calibre abnormalities.
pk acts at the level of the sebaceous gland, disturbing the normal process of hair eruption. The roles of the internal root sheath, external root sheath and the sebaceous gland in hair eruption are discussed.
The abnormal epidermal layer in soc/soc and Ve /+ skin also disturbs hair eruption to a small extent. The resulting abnormalities this causes in hair shaft formation are compared with those found pk/pk samples and also with the similar effects of faulty hair movement in the hair waving mutants. An effect on pigmentation is also described.
The chemistry of keratinization appears to be normal in all these mutants.     

Coat color dilution in mice because of inactivation of the melanoma antigen MART-1

Melanoma antigen recognized by T cells 1 (MART-1) is a melanoma-specific antigen, which has been thoroughly studied in the context of immunotherapy against malignant melanoma and which is found only in the pigment cell lineage. However, its exact function and involvement in pigmentation is not clearly understood. Melanoma antigen recognized by T cells 1 has been shown to interact with the melanosomal proteins Pmel17 and OA1. To understand the function of MART-1 in pigmentation, we developed a new knockout mouse model. Mice deficient in MART-1 are viable, but loss of MART-1 leads to a coat color phenotype, with a reduction in total melanin content of the skin and hair. Lack of MART-1 did not affect localization of melanocyte-specific proteins nor maturation of Pmel17. Melanosomes of hair follicle melanocytes in MART-1 knockout mice displayed morphological abnormalities, which were exclusive to stage III and IV melanosomes. In conclusion, our results suggest that MART-1 is a pigmentation gene that is required for melanosome biogenesis and/or maintenance.     

Coat Color Variation and Pigmentation Gene Expression in Rhesus Macaques (Macaca mulatta)

Light-dark coat color variation is a common aspect of color diversity within and across mammalian taxa. This variation in pelage brightness is associated with aspects of evolutionary ecology, particularly for primates, but little is known about the genetic mechanisms underlying light-dark differences in pelage pigmentation. Previous work, focusing particularly on macaques (Genus Macaca), has found no clear relationship between color variation and coding sequences of key pigmentation genes. This suggests that other loci and/or gene regulatory differences underlie this variation and raises the question of how patterns of gene expression differ in light verses dark hair follicles. Here, we examine relative expression levels of pigmentation genes in hair follicles from free-ranging rhesus macaques (Macaca mulatta) showing stark light-dark coat color variation. We quantified the brightness (reflectance) of plucked hair tufts using a spectrophotometer. We extracted RNA from the follicles and used quantitative RT-PCR to measure the relative amounts of gene product (mRNA) for seven candidate pigmentation genes (MITF, MC1R, MGRN1, ATRN, SLC24A5, TYRP1, and DCT). Expression values were normalized with the house-keeping gene ACTB. All candidate genes were expressed at similar levels in dark, intermediate, and light hair, and thus, light-dark variation in macaque coat color is unlikely to be due to differences in the expression of these key pigmentation genes. This study represents the first examination of gene expression and natural color variation in a non-human primate population. Our results indicate that even in a system, like pigmentation, where a candidate-gene approach is promising, identifying important intra-specific gene regulatory differences remains challenging.     

哺乳动物毛色调控机制及其适应性进化研究进展

哺乳动物类群呈现出的丰富毛色是引人注目的一种生物现象,是研究和理解哺乳动物适应性进化的理想模型之一。哺乳动物的毛色多态在躲避天敌、捕食、求偶及抵御紫外线等方面都具有重要作用。哺乳动物毛发的色素化过程由体内黑色素的数量、质量和分布状况所决定。黑色素的形成过程复杂,包括黑素细胞的分化、成熟,黑素体等细胞器的形态发生及黑色素在黑素细胞中的合成代谢和转运等过程;而在细胞色素化的每个阶段/时相都伴随着一些重要功能基因的参与,并通过基因之间的相互作用形成了黑色素生物代谢的复杂调控网络,进而形成不同的毛色有助于哺乳动物适应不同生存环境。对哺乳动物不同毛色形成机制的探究一直以来都是遗传学及进化生物学的重要研究领域和聚焦热点。本文综述了哺乳动物毛色色素化过程的主要分子机制以及毛色适应性进化的遗传基础,以期为哺乳动物毛色多态及其适应性进化的分子机制研究提供参考。     

The effect of methyl-containing supplements during pregnancy on the phenotypic modification of offspring hair color in rats

The effect of methyl supplements to the diet of pregnant homozygous (AAHH) female rats with agouti coat color mated with homozygous (aahh) males on the phenotypic modification of the coat color of their heterozygous offspring (AaHh) has been studied. Comparative morphological analysis of the main parameters of hair that determine coat color, including the total length of hairs of different types and the length of the upper black (eumelanin) and light (pheomelanin) parts of awn hairs has been performed. The pattern of pigment granule distribution among hair layers has been analyzed. The melanin content of the hair has been determined using electron spin resonance (ESR). Although all offspring have a typical agouti coat color (alternating black and light portions of hair), 39% of them have a darker coat color than control and other experimental rats have. The main differences between the offspring with darkened and standard coat colors are accounted for by the ratio between the eumelanin and pheomelanin portions of awn hairs. In darkened offspring, this ratio is significantly higher than in control rats. The possible mechanisms of the phenotypic modification of agouti coat color in experimental animals are discussed.     

Sequence divergence at chalcone synthase gene in pigmented seed coat soybean mutants of the Inhibitor locus

Seed coat color in soybeans is determined by the I (Inhibitor) locus. The dominant I allele inhibits seed coat pigmentation, and it has been suggested that there is a correlation between the inhibition of pigmentation by the I allele and chalcone synthase (CHS) gene silencing in the seed coat. Analysis of spontaneous mutations from I to i has shown that these mutations are closely related to the deletion of one of the CHS genes (designated ICHS1). In soybeans with the I/I genotype (cv. Miyagi shirome), a truncated form of the CHS gene (CHS3) is located in an inverse orientation 680 bp upstream of ICHS1, and it was previously suggested that the truncated CHS3- ICHS1 cluster might be involved in CHS gene silencing in the seed coat. In the current study, the truncated CHS3- ICHS1 cluster was compared with the corresponding region of pigmented seed coat mutants in which I had changed to i in Miyagi shirome and in the strain Karikei 584. In the Karikei 584 mutant, the truncated CHS3-ICHS1 cluster was retained and the sequence diverged at a point immediately upstream (32 bp) of this cluster. The sequences upstream of the points of divergence in both mutants almost perfectly matched a part of the registered sequence in a soybean BAC clone containing the soybean cyst nematode resistance-associated gene, and inspection of the sequences suggested that the sequence divergence of the CHS gene in the Karikei 584 and Miyagi shirome mutants was due to an unequal crossing-over via 4-bp or 5-bp short repeats, respectively.     

The effect of methyl supplements during pregnancy on the phenotypic modification of offspring agouti coat color in rats

The effect of methyl supplements to the diet of pregnant homozygous (AAHH) female rats with agouti coat color mated with homozygous (aahh) males on the phenotypic modification of the coat color of their heterozygous offspring (AaHh) has been studied. Comparative morphological analysis of the main parameters of hair that determine coat color, including the total length of hairs of different types and the length of the upper black (eumelanin) and light (pheomelanin) parts of awn hairs has been performed. The pattern of pigment granule distribution among hair layers has been analyzed. The melanin content of the hair has been determined using electron spin resonance (ESR). Although all offspring have a typical agouti coat color (alternating black and light portions of hair), 39% of them have a darker coat color than control and other experimental rats have. The main differences between the offspring with darkened and standard coat colors are accounted for by the ratio between the eumelanin and pheomelanin portions of awn hairs. In darkened offspring, this ratio is significantly higher than in control rats. The possible mechanisms of the phenotypic modification of agouti coat color in experimental animals are discussed.     

Chromosomal assignment of the canine melanophilin gene (MLPH): a candidate gene for coat color dilution in Pinschers

Pinschers affected by coat color dilution show a specific pigmentation phenotype. The dilute pigmentation phenotype leads to a silver-blue appearance of the eumelanin-containing fur and a pale sandy color of pheomelanin-containing fur. In Pinscher breeding, dilute black-and-tan dogs are called "blue," and dilute red or brown animals are termed "fawn" or "Isabella fawn." Coat color dilution in Pinschers is sometimes accompanied by hair loss and a recurrent infection of the hair follicles. In human and mice, several well-characterized genes are responsible for similar pigment variations. To investigate the genetic cause of the coat color dilution in Pinschers, we isolated BAC clones containing the canine ortholog of the known murine color dilution gene Mlph. RH mapping of the canine MLPH gene was performed using an STS marker derived from BAC sequences. Additionally, one MLPH BAC clone was used as probe for FISH mapping, and the canine MLPH gene was assigned to CFA25q24.     

The genetics of coat colors in the mongolian gerbil (Meriones unguiculatus)

Genetic studies demonstrated three loci controlling coat colors in the Mongolian gerbil. F1 hybrids of white gerbils with red eyes and agouti gerbils with wild coat color had the agouti coat color. The segregating ratio of agouti and white in the F2 generation was 3:1. In the backcross (BC) generation (white x F1), the ratio of the agouti and white coat colors was 1:1. Next, inheritance of the agouti coat color was investigated. Matings between agouti and non-agouti (black) gerbils produced only agouti gerbils. In the F2 generation, the ratio of agouti to non-agouti (black) was 3:1. There was no distortion in the sex ratios within each coat color in the F1, F2 and BC generations. This indicated that the white coat color of gerbils is governed by an autosomal recessive gene which should be named the c allele of the c (albino) locus controlling pigmentation, and the agouti coat color is controlled by an autosomal dominant gene which might be named the A allele of the A (agouti) locus controlling pigmentation patterns in the hair. The occurrence of the black gerbil demonstrated clearly the existence of the b (brown) locus, and it clearly indicated that the coat colors of gerbils can basically be explained by a, b, and c loci as in mice and rats.     

Human hair melanins: what we have learned and have not learned from mouse coat color pigmentation

Hair pigmentation is one of the most conspicuous phenotypes in humans. Melanocytes produce two distinct types of melanin pigment: brown to black, indolic eumelanin and yellow to reddish brown, sulfur‐containing pheomelanin. Biochemically, the precursor tyrosine and the key enzyme tyrosinase and the tyrosinase‐related proteins are involved in eumelanogenesis, while only the additional presence of cysteine is necessary for pheomelanogenesis. Other important proteins involved in melanogenesis include P protein, MATP protein, α‐MSH, agouti signaling protein (ASIP), MC1R (the receptor for MSH and ASIP), and SLC7A11, a cystine transporter. Many studies have examined the effects of loss‐of‐function mutations of those proteins on mouse coat color pigmentation. In contrast, much less is known regarding the effects of mutations of the corresponding proteins on human hair pigmentation except for MC1R polymorphisms that lead to pheomelanogenesis. This perspective will discuss what we have/have not learned from mouse coat color pigmentation, with special emphasis on the significant roles of pH and the level of cysteine in melanosomes in controlling melanogenesis. Based on these data, a hypothesis is proposed to explain the diversity of human hair pigmentation.     

Effects of monorecessive and double recessive mutations affecting coat color on the monoamine content of the brain of the American mink (<Emphasis Type="Italic">Mustela vison</Emphasis> Schreber, 1777)

The effects of mutations affecting the coat color on the dopamine, noradrenaline, and serotonin contents of the hypothalamus and brainstem of the American mink have been studied. The sample comprised standard (+/+) and mutant minks, including the monorecessive pastel (b/b), silver-blue (p/p), and white hedlund (h/h) and the combination double recessive sapphire (a/a p/p) and pearl (k/k p/p) ones. The dopamine content of the brainstem of the monorecessive pastel (b/b) and silver-blue (p/p) minks has been found to be higher than in standard (+/+) minks. Conversely, the homozigosity for two coat color loci in double recessive pearl minks (k/k p/p) significantly decreases the noradrenaline and serotonin contents of the hypothalamus. In addition, monorecessive and double recessive minks differ from each other in the serotonin contents of the midbrain and medulla.     

The we gene is a modifier of the wal gene in mice

Interaction of gene wellhaarig (we) with genes waved alopecia (wal) and hairless (hr) was studied in mice. The mutant gene we is responsible for the development of a specific waved coat in homozygotes. Homozygous mice carrying mutant gene wal also have a wavy coat, though a partial alopecia develops with time in these animals. In homozygotes for the hr gene, hair loss is observed beginning from the age of ten days. A series of crosses we/we and wal/wal yielded animals with we/+wal/wal and we/we wal/wal genotypes. In mice we/+wal/wal carrying gene we at a single dose, alopecia is accelerated significantly as compared to the single-dose homozygotes +/+wal/wal. In we/we wal/wal mice, alopecia starts earlier than in we/+wal/wal mice; by the age of one month, the double homozygotes are almost hairless except for small body areas covered with a sparse coat. In addition, curliness of the first-generation hair in mice we/we wal/wal is much more expressed than in +/+wal/wal and we/we+/+ mice. The obtained evidence suggests that the we gene is a modifier of the wal gene because the former enhances the effects of the wal gene, which is confirmed by the earlier onset of alopecia and progression of the latter in mice having the we/+wal/wal genotype and especially in we/we wal/wal animals. The we/we hr/+ mice do not differ in coat from we/we+/+ mice; in both cases, the coat is wavy. The coat of double homozygotes we/we hr/hr, is similar to that of we/we+/+ mice until ten days of age, when the signs of alopecia appear. By the age of 21 days, mice we/we hr/hr have lost their coat completely like mice +/+ hr/hr. Hence, the we gene is a modifier of the wal gene though it does not interact with hr gene during the coat formation.     

Variation of the melanocortin 1 receptor gene in the macaques

Melanocortin 1 receptor (MC1R), a G-coupled seven-transmembrane receptor protein, plays a key role in the regulation of melanin synthesis in mammals. Sequence variation of the MC1R gene (MC1R) has been associated with pigmentation phenotypes in humans and in several animal species. The macaques (genus Macaca) are known to show a marked inter-specific variation in coat color although the causative genetic variation remains unclear. We investigated nucleotide sequences of the MC1R in 67 individuals of 18 macaque species with different coat color phenotypes including black and agouti. Twenty-eight amino acid replacements were identified in the macaques, but none of these amino acid replacements could explain the black coat color of Macaca silenus and the Sulawesi macaque species. Our molecular evolutionary analysis has revealed that nonsynonymous substitution/synonymous substitution (dN/dS) ratio of the MC1R has not been uniform in the macaque groups and, moreover, their coat color and dN/dS ratio were not related. These results suggest that the MC1R is unlikely to be responsible for the coat color variation of the macaques and functions of MC1R other than pigmentation might be associated with the different selective pressures on the MC1R in macaques.     

Reverse genetic screen for loss‐of‐function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle

In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10‐bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein. Recessive damaging mutations in the MLPH gene are well known to cause skin, hair, coat or plumage color dilution phenotypes in numerous species, including human, mice, dog, cat, mink, rabbit, chicken and quail. Large‐scale array genotyping undertaken to identify p.Glu32Aspfs*1 homozygous mutant animals revealed a mutation frequency of 5% in the breed and allowed for the identification of 10 homozygous mutants. As expression of a colored coat requires at least one wild‐type allele at the co‐dominant Roan locus encoded by the KIT ligand gene (KITLG), homozygous mutants for p.Ala227Asp corresponding with the missense mutation were excluded. The six remaining colored calves displayed a distinctive dilution phenotype as anticipated. This new coat color was named ‘cool gray’. It is the first damaging mutation in the MLPH gene described in cattle and extends the already long list of species with diluted color due to recessive mutations in MLPH and broadens the color palette of gray in this breed.