Canine coat pigmentation genetics: a review.

Our understanding of canine coat colour genetics and the associated health implications is developing rapidly. To date, there are 15 genes with known roles in canine coat colour phenotypes. Many coat phenotypes result from complex and/or epistatic genetic interactions among variants within and between loci, some of which remain unidentified. Some genes involved in canine pigmentation have been linked to aural, visual and neurological impairments. Consequently, coat pigmentation in the domestic dog retains considerable ethical and economic interest. In this paper we discuss coat colour phenotypes in the domestic dog, the genes and variants responsible for these phenotypes and any proven coat colour-associated health effects.

Equine vitiligo-like depigmentation in grey horses is related to genes involved in immune response and tumor metastasis.

BACKGROUND: In horses, the autoimmune disease vitiligo is characterized by the loss of melanocytes and results in patchy depigmentation of the skin around the eyes, muzzle and the perianal region. Vitiligo-like depigmentation occurs predominantly in horses displaying the grey coat colour and is observed at a prevalence level of 26.0-67.0% in grey horses compared with only 0.8-3.5% in non-grey horses. While the polygenetic background of this complex disease is well documented in humans, the underlying candidate genes for this skin disorder in horses remain unknown. In this study we aim to perform a genome-wide association study (GWAS) for identifying putative candidate loci for vitiligo-like depigmentation in horses. METHODS: In the current study, we performed a GWAS analysis using high-density 670 k single nucleotide polymorphism (SNP) data from 152 Lipizzan and 104 Noriker horses, which were phenotyped for vitiligo-like depigmentation by visual inspection. After quality control 376,219 SNPs remained for analyses, the genome-wide Bonferroni corrected significance level was p < 1.33e-7. RESULTS: We identified seven candidate genes on four chromosomes (ECA1, ECA13, ECA17, ECA20) putatively involved in vitiligo pathogenesis in grey horses. The highlighted genes PHF11, SETDB2, CARHSP1 and LITAFD, are associated with the innate immune system, while the genes RCBTB1, LITAFD, NUBPL, PTP4A1, play a role in tumor suppression and metastasis. The antagonistic pathogenesis of vitiligo in relation to cancer specific enhanced cell motility and/or metastasis on typical melanoma predilection sites underlines a plausible involvement of RCBTB1, LITAFD, NUBPL, and PTP4A1. CONCLUSIONS: The proposed candidate genes for equine vitiligo-like depigmentation, indicate an antagonistic relation between vitiligo and tumor metastasis in a horse population with higher incidence of melanoma. Further replication and expression studies should lead to a better understanding of this skin disorder in horses.

Genome-wide association studies for iris pigmentation and heterochromia patterns in Large White pigs.

Eye colour genetics have been extensively studied in humans since the rediscovery of Mendel's laws. This trait was first interpreted using simplistic genetic models but soon it was realised that it is more complex. In this study, we analysed eye colour variability in a Large White pig population (n = 897) and report the results of GWASs based on several comparisons including pigs having four main eye colour categories (three with both pigmented eyes of different brown grades: pale, 17.9%; medium, 14.8%; and dark, 54.3%; another one with both eyes completely depigmented, 3.8%) and heterochromia patterns (heterochromia iridis - depigmented iris sectors in pigmented irises, 3.2%; heterochromia iridum - one whole eye iris of depigmented phenotype and the other eye with the iris completely pigmented, 5.9%). Pigs were genotyped with the Illumina PorcineSNP60 BeadChip and GEMMA was used for the association analyses. The results indicated that SLC45A2 (on chromosome 16, SSC16), EDNRB (SSC11) and KITLG (SSC5) affect the different grades of brown pigmentation of the eyes, the bilateral eye depigmentation defect and the heterochromia iridis defect recorded in this white pig population respectively. These genes are involved in several mechanisms affecting pigmentation. Significant associations for the eye depigmented patterns were also identified for SNPs on two SSC4 regions (including two candidate genes: NOTCH2 and PREX2) and on SSC6, SSC8 and SSC14 (including COL17A1 as candidate gene). This study provided useful information to understand eye pigmentation mechanisms, further valuing the pig as animal model to study complex phenotypes in humans.

Progressive retrocorneal pigmentation in dogs: A clinical report of 34 cases.

OBJECTIVES: To describe the signalment, ophthalmic examination findings, and follow-up of dogs affected with a previously unreported retrocorneal pigmentary lesion. MATERIALS AND METHODS: Retrospective record evaluation spanning 2009-2019. RESULTS: Retrocorneal pigmentary lesions were described in 34 patients (46 eyes). German Shepherds (n = 7), Jack Russel terriers (n = 5), and terrier crosses (n = 4) made up 16/34 (47.1%) of the cases. The mean age was 13.5 years (range 1.4-14.2 years), and 16/30 (53.3%) dogs were female. Most dogs were affected unilaterally (22/34 (64.7%)), the others bilaterally, and 5/34 (14.7%) were referred for it while the others were incidentally diagnosed. The lesions affected the ventral, peripheral, inner cornea and had a round/undulated leading edge. The number of corneal clock hours affected was known for 41/46 (89.1%) eyes and involved 1-3 clock hours in 32/41 (78.1%) eyes, 4-6 in 6/41 (14.6%), 7-9 in 2/41 (4.9%), and 10 in 1/41 (2.4%). The central cornea was affected in 9/46 (19.6%) eyes, and in 5/9 (55.6%), the median corneal clarity score was G2 (scale: G0-G4). The commonest additional findings included free-floating uveal cysts (11/34 dogs, 32.4%), cataracts (6/34 dogs, 17.6%), and primary glaucoma (5/34 dogs, 14.7%). Gonioscopy was available in 16/34 (47.1%) dogs and was normal except in primary glaucoma cases. Follow-up was documented in 13/34 (38.2%) dogs with a mean follow-up of 17 months (range: 5-26 months). Lesion progression was documented in 6/13 (46.2%) dogs. CONCLUSIONS: Retrocorneal pigmentation occurs as a slowly progressive lesion of older dogs that could impact vision. Histological studies of affected eyes are warranted.

Autoimmune diseases affecting skin melanocytes in dogs, cats and horses: vitiligo and the uveodermatological syndrome: a comprehensive review.

Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes.In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans.Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness.

Renal pigmentation due to chronic bismuth administration in a rhesus macaque (Macaca mulatta).

Renal pigmentation due to the administration of exogenous compounds is an uncommon finding in most species. This report describes renal pigmentation and intranuclear inclusions of the proximal convoluted tubules due to chronic bismuth administration in a rhesus macaque. An 11-year-old Indian-origin rhesus macaque with a medical history of chronic intermittent vomiting had been treated with bismuth subsalicylate, famotidine, and omeprazole singly or in combination over the course of 8 years. At necropsy, the renal cortices were diffusely dark green to black. Light and electron microscopy revealed intranuclear inclusions within the majority of renal proximal tubular epithelial cells. These inclusions appeared magenta to brown when stained with hematoxylin and eosin and were negative by the Ziehl-Neelsen acid-fast stain. Elemental analysis performed on frozen kidney measured bismuth levels to be markedly elevated at 110.6 ppm, approximately 500 to 1000 times acceptable limits. To our knowledge, this is the first report of renal bismuth deposition in a rhesus macaque resulting in renal pigmentation and intranuclear inclusions.

Uveodermatologic syndrome concurrent with keratoconjunctivitis sicca in a miniature poodle dog.

A 5-year-old, intact female miniature poodle dog was presented with chronic ophthalmic problems, facial poliosis, nasal depigmentation and multiple areas of alopecia over the trunk. Bilateral uveitis preceded dermatologic signs by 5 months and gradually worsened. The dog was diagnosed as having uveodermatologic syndrome (UDS) concurrent with keratoconjunctivitis sicca (KCS). Treatment with immunosuppressive drugs resolved the dermatologic lesions, but uveitis continued to progress.

Syndrome uvéodermatologique concomitant à une kératoconjonctivite sèche chez un caniche miniature. Une chienne caniche miniature intacte âgée de 5 ans a été présentée avec des problèmes ophtalmiques chroniques, une poliose faciale, une dépigmentation nasale et plusieurs plaques d'alopécie sur le tronc. L'uvéite bilatérale a précédé les signes dermatologiques 5 mois auparavant et elle s'est graduellement aggravée. La chienne a été diagnostiquée comme atteinte du syndrome uvéodermatologique concomitant à une kératoconjonctivite sèche. Le traitement avec des immunodépresseurs a résolu les lésions dermatologiques, mais l'uvéite a continué de progresser.(Traduit par Isabelle Vallières).

Massive bleaching of coral reefs induced by the 2010 ENSO, Puerto Cabello, Venezuela.

El Niño Southern Oscillation (ENSO) has generated global coral massive bleaching. The aim of this work was to evaluate the massive bleaching of coral reefs in Puerto Cabello, Venezuela derived from ENSO 2010. We evaluated the bleaching of reefs at five localities both at three and five meter depth. The coral cover and densities of colonies were estimated. We recorded living coral cover, number and diameter of bleached and non-bleached colonies of each coral species. The colonies were classified according to the proportion of bleached area. Satellite images (Modis Scar) were analyzed for chlorophyll-a concentration and temperature in August, September, October and November from 2008-2010. Precipitation, wind speed and air temperature information was evaluated in meteorological data for 2009 and 2010. A total of 58.3% of colonies, belonging to 11 hexacoral species, were affected and the greatest responses were observed in Colpophyllia natans, Montastraea annularis and Montastraeafaveolata. The most affected localities were closer to the mainland and had a bleached proportion up to 62.73+/-36.55%, with the highest proportion of affected colonies, whereas the farthest locality showed 20.25+/-14.00% bleached and the smallest proportion. The salinity in situ varied between 30 and 33ppm and high levels of turbidity were observed. According to the satellite images, in 2010 the surface water temperature reached 31 degree C in August, September and October, and resulted higher than those registered in 2008 and 2009. Regionally, chlorophyll values were higher in 2010 than in 2008 and 2009. The meteorological data indicated that precipitation in November 2010 was three times higher than in November 2009. Massive coral bleaching occurred due to a three month period of high temperatures followed by one month of intense ENSO-associated precipitation. However, this latter factor was likely the trigger because of the bleaching gradient observed.

Uveodermatologic syndrome in a rat terrier.

A 4 yr old intact male rat terrier presented with severe bilateral nonresponsive panuveitis. Bilateral uveitis, blepharospasm, conjunctival hyperemia, diffuse corneal edema, peripheral bullous retinal detachment, and secondary ocular hypertension were noted. Ocular lesions progressed despite aggressive medical treatment and were followed by cutaneous depigmentation and crusting along the nasal planum. Intensive oral and topical anti-inflammatory and topical antiglaucoma medications were administered, but the ocular disease progressed. A bilateral enucleation was performed. Uveodermatologic syndrome was diagnosed from histopathologic examination of a skin biopsy as well as histopathology of both globes after bilateral enucleation. To maintain control of the dermatologic lesions, oral azathioprine was initiated, but it was not well tolerated by this patient. Immunosuppressive doses of oral cyclosporine and anti-inflammatory doses of oral prednisone were used to control the depigmentation and crusting skin lesions.

Experimentally induced melanin-like pigmentation (thesaurismosis) related to acorn ingestion in Nero Siciliano pigs.

In this study, an experimental challenge was carried out by feeding Nero Siciliano pigs with acorn to evoke melanin-like pigmentation and support the hypothesis that it is caused by ingested material. Twelve pigs were studied, 6 fed with acorns and 6 fed commercial feed. At slaughter, all the animals fed on acorns showed black discolouration of almost all lymph nodes. The lymph nodes were normal in size and shape. Histochemical tests performed on tissues allowed us to identify and differentiate the pigment. Immunohistochemical staining for macrophage markers showed macrophages containing a variable amount of melanin-like granules. Our data, and the well-known steps of melanin formation, confirm that swine enzymes could act on phenolic substances found in acorns.

Case Series: Gene Expression Analysis in Canine Vogt-Koyanagi-Harada/Uveodermatologic Syndrome and Vitiligo Reveals Conserved Immunopathogenesis Pathways Between Dog and Human Autoimmune Pigmentary Disorders.

Vogt-Koyanagi-Harada syndrome (VKH) and vitiligo are autoimmune diseases that target melanocytes. VKH affects several organs such as the skin, hair follicle, eyes, ears, and meninges, whereas vitiligo is often limited to the skin and mucosa. Many studies have identified immune genes, pathways and cells that drive the pathogeneses of VKH and vitiligo, including interleukins, chemokines, cytotoxic T-cells, and other leukocytes. Here, we present case studies of 2 canines with VKH and 1 with vitiligo, which occurred spontaneously in client-owned companion dogs. We performed comparative transcriptomics and immunohistochemistry studies on lesional skin biopsies from these cases in order to determine if the immunopathogenesis of autoimmune responses against melanocytes are conserved. In dogs, we found enrichment of T cell gene signatures, with upregulation of IFNG, TNF, PRF1, IL15, CTSW, CXCL10, and CCL5 in both VKH and vitiligo in dogs compared to healthy controls. Similar findings were reported in humans, suggesting that these genes play a role in the pathogenesis of spontaneous VKH and vitiligo. T cell-associated genes, including FOXP3 and TBX21, were enriched, while IGFBP5, FOXO1, and PECAM1 were decreased compared to healthy controls. Further, we identified TGFB3, SFRP2, and CXCL7 as additional potential drivers of autoimmune pigmentary disorders. Future studies exploring the immunopathogenesis of spontaneous autoimmunity will expand our understanding of these disorders, and will be useful in developing targeted therapies, repurposing drugs for veterinary and human medicine, and predicting disease prognosis and treatment response.

Lateral line depigmentation (LLD) in channel catfish, Ictalurus punctatus (Rafinesque).

Head and lateral line erosion (HLLE) is a chronic dermatopathy affecting a number of fish that presents as depigmented skin along the lateral line system of the trunk and head. We present microbiological, immunological and histopathological features of this lesion in channel catfish, Ictalurus punctatus (Rafinesque), that developed after exposure to a chronic nutritional stress. Depigmention was limited to skin that was adjacent to the lateral line. The epidermis of affected fish was thin and reduced to a one-cell-thick layer over the lateral line. Melanocytes were depleted at the dermo-epidermal junction and formed aggregates in the epidermis. Innate immunity was weaker in affected fish than that previously measured in well-fed channel catfish. Because the pathology and apparent aetiology of HLLE described in various fish species are highly variable, HLLE appears to be a clinical sign, rather than a disease or syndrome. Thus, we propose that this clinical sign be referred to as lateral line depigmentation (LLD), because this description more accurately encompasses all cases of this presentation reported in fish. As nutritional requirements of channel catfish and lateral line neuroanatomy are well-known, the ability to reproducibly induce LLD in this species could provide a useful model for understanding its pathogenesis.

Uveodermatologic syndrome in an Akita.

An 8-year-old, spayed, female Japanese Akita was presented for acute blindness, cloudy eyes, and squinting. A presumptive diagnosis of uveodermatologic syndrome was made. Therapy with oral prednisone, topical prednisolone, and oral azathioprine was successful in eliminating most of the clinical signs and the Akita now has complete restoration of vision.

Dermal melanocytosis in Japanese monkeys (Macaca fuscata).

The skin of Japanese monkeys (Macaca fuscata) shows diffuse discolorations resembling human dermal melanocytosis. Very few laboratory animals have melanocytes in the dermis. The purpose of this study was to clarify the dermatologic characteristics of Japanese monkeys in terms of gross appearance, skin color, and histopathologic findings. A colorimeter was used to record the skin colors of pigmented and nonpigmented sites. Tissue specimens obtained from both types of sites were examined histopathologically. All animals examined had pigmented sites on their bodies, and the discolorations extended over 25% to 33% of the body surface. The colorimeter could detect differences in skin color due to dermal melanocytosis. All parameters of the colorimetric systems used (Yxy, L*a*b*, and L*C*h* systems) demonstrated significant differences between pigmented and nonpigmented sites. In pigmented sites, the epidermis lacked melanocytes, but the dermis had numerous melanocytes with abundant melanin. Activated melanocytes with well-developed dendrites were distributed throughout the upper part of the dermal layer. Melanocytes were not arranged in clusters, and elastic and collagen fibers in the dermis showed no histological abnormalities. Nonpigmented sites lacked melanin granules in both the epidermis and dermis. This study revealed that gross dermal melanocytosis correlated well with colorimetric results and histopathologic findings. These findings suggest that the pigmentation of Japanese monkeys is equivalent to dermal melanocytosis in humans, to the end that Japanese monkeys may be a useful animal model for investigating dermal melanogenesis.

Unilateral uveitis in a dog with uveodermatologic syndrome.

CASE DESCRIPTION: A 7-year-old Siberian Husky-type dog with heterochromia irides was evaluated because of signs of pain associated with the right eye. CLINICAL FINDINGS: Unilateral panuveitis, iris bombé, and secondary glaucoma were detected in the right eye. Tear production was low bilaterally. Facial and truncal poliosis and vitiligo were also evident; skin biopsy specimens were obtained from the nasal planum. Uveodermatologic syndrome was diagnosed on the basis of histopathologic findings of a lichenoid interface dermatitis and pigmentary incontinence within the dermis. Immunohistochemical analysis was performed on skin samples retrospectively, and findings were inconclusive. TREATMENT AND OUTCOME: Treatment involved topical (ocular) and oral administration of corticosteroids, oral administration of azathioprine, and topical (ocular) administration of a carbonic anhydrase inhibitor and a lacrimostimulant. The secondary glaucoma was refractory to treatment, and the right eye was enucleated. Uveodermatologic syndrome was confirmed via histologic examination of ocular tissues. The left eye remained free of inflammation 16 months after the initial diagnosis. The periocular skin and skin of the nose partially regained pigment, but the hair did not. CLINICAL RELEVANCE: Some breeds in which uveodermatologic syndrome has been reported (eg, Siberian Huskies, Old English Sheepdogs, Australian Shepherds, and Shetland Sheepdogs) often have heterochromia irides. This case highlights the fact that dogs with asymmetric uveal pigmentation may have unilateral ocular changes; therefore, uveodermatologic syndrome should not be excluded as a differential diagnosis on the basis of unilateral clinical signs.

Iatrogenic hyperadrenocorticism in 12 cats.

Iatrogenic hyperadrenocorticism is an extremely rare condition in cats. Twelve cats with a medical history of progressive skin lesions and long-term treatment with corticosteroids were retrospectively studied. Noncutaneous signs in the cats were variable and included anorexia, lethargy, polydipsia, polyuria, and atrophy of the thigh muscles. Laboratory abnormalities included leukocytosis, elevated alanine aminotransferase levels, and hyperglycemia. Transient diabetes mellitus was a secondary complication in four cats, and transient hypothyroidism was suspected in four cats. The mean time for regression of signs was 4.9 months after corticosteroid withdrawal.

Vitiligo in equine: a four-year case study of a roan horse - case report / [Vitiligo em equinos: um estudo de caso de quatro anos de um cavalo roan - relato de caso]

Vitiligo is a dermatological disease affecting both animals and humans. It is characterized by depigmented macules of varying shape and size, originated from melanocyte destruction. Even though there are some theories tackling causation, disease etiopathology is not yet certain. Moreover, lesion areas can either increase or diminish over time, and therefore, available treatment alternatives tend to prove inconsistencies. No epidemiological data or registered cases were found for equines in Brazil. The horse in this case description displayed depigmentation areas in facial regions, including upper lip, nose and lips. However, the individual did not happen to develop any systemic alteration. Through clinical evaluation, backed by a histopathological exam, a definitive vitiligo diagnosis was obtained. However, no therapeutic plan was stipulated. The animal was accompanied for four years, during which period some affected areas diminished while others increased in size. In addition, emergence of new skin lesions was also observed during the time the animal was studied. Overall, this disease does not display alterations to organism functionality, only aesthetic changes. Therefore, treatment plans may vary from case to case, occasionally being even ruled out.(AU)

O vitiligo é uma doença dermatológica que pode afetar animais e humanos. Caracteriza-se por áreas despigmentadas, de formas e tamanhos variáveis, que surgem devido a destruição dos melanócitos. Existem algumas teorias que tentam explicar a etiopatogenia da doença, entretanto ainda não é totalmente esclarecida. As lesões podem aumentar ou diminuir com o tempo, por isso os tratamentos disponíveis são inconsistentes. Não foram encontrados dados epidemiológicos ou relatos de vitiligo em cavalos no Brasil. O equino deste relato apresentava lesões despigmentadas na região da face, incluindo pálpebras, narina e lábios, sem alterações sistêmicas. Por meio da avaliação clínica em conjunto com o exame histopatológico obteve-se o diagnóstico definitivo de vitiligo. Não foi instituído nenhuma terapia, e o equino foi acompanhado durante quatro anos. Durante esse período algumas lesões diminuíram e outras aumentaram de tamanho sendo também observado o aparecimento de novas lesões. O vitiligo não traz alterações sistêmicas, apenas mudanças estéticas, por isso a escolha pelo tratamento dependerá de cada caso.(AU)

Pigmentation development, defects, and patterning in summer flounder (Paralichthys dentatus).

Flounders offer unique opportunities to study the cytological basis of vertebrate pigmentation. Individual skin pigment cells are clearly visible at hatching, and flounder ontogeny includes a dramatic shift in overall pigmentation (from symmetrical to asymmetrical) during metamorphosis. Moreover, several types of malpigmentation occur in hatchery populations; although much effort has gone into reducing the frequency of such defects, their etiology remains poorly understood, and they have rarely been described at the cellular level. In this paper, we use light and fluorescence microscopy to describe the cytological basis of normal developmental changes and of common types of malpigmentation. We then discuss the implications of these observations for underlying patterning mechanisms.

A retrospective survey of ocular abnormalities in pugs: 130 cases.

OBJECTIVES: To determine the types and frequency of ophthalmic findings in pugs. MATERIALS AND METHODS: Retrospective analysis of case records of pugs presented to an ophthalmology unit between 2001 and 2012. Ophthalmological findings were correlated with age, gender, presenting signs and time of onset of disease. RESULTS: In total, 130 pugs (258 eyes) with a mean (±sd) age of 2 · 8 (±2 · 87) years were examined. Ocular abnormalities identified included keratoconjunctivitis sicca (n = 39 eyes), macroblepharon (n = 258 eyes), entropion (n = 258 eyes), distichiasis (n = 56 eyes), ectopic cilia (n = 8 eyes), conjunctivitis (n = 88 eyes), corneal pigmentation (n = 101 eyes), opacity (n = 63 eyes), ulceration (n = 46 eyes), vascularisation (n = 35 eyes), iris-to-iris persistent pupillary membranes (n = 21 eyes) and cataract (n = 18). Keratoconjunctivitis sicca was significantly associated with the presence of corneal pigmentation (P = 0 · 007 for left eyes; P = 0 · 043 for right eyes). However corneal pigmentation was also identified in pugs (n = 61) without keratoconjunctivitis sicca. There was a significant influence of ectopic cilia on corneal ulceration (P < 0 · 001). Younger dogs (mean age, 1 · 28 (±0 · 45) years) were significantly more affected by distichiasis. CLINICAL SIGNIFICANCE: The high number of cases of corneal pigmentation without keratoconjunctivitis sicca suggests that there may be additional yet undetermined factors involved in the development of corneal pigmentation in pugs.

Delayed-amelanotic (DAM or Smyth) chicken: melanocyte dysfunction in vivo and in vitro.

Chickens of the autoimmune delayed-amelanotic (DAM or Smyth) line develop postnatal feather amelanosis and severe visual defects, both of which are presumed to be due to a dysfunction of melanocytes and a subsequent autoimmune response that eliminates pigment cells. In this report we elucidate further the melanocytic defect. We present a morphologic analysis of the mildly affected erratic (eDAM) group of Smyth chicken whose partial depigmentation and lack of visual impairment resemble human vitiligo more so than do the complete amelanosis and blindness in the classical Smyth line. Histologically, the sequential events leading to amelanosis in the young Smyth chicken occur simultaneously in the feathers of adult eDAM Smyth chickens, and the infiltration of the feather pulp with mononuclear leukocytes correlates with the extent of local pigmentary abnormality. Cytochemical localizations of dopa-oxidase and acid-phosphatase activities in eDAM feather melanocytes suggest that melanogenesis and autophagocytosis of melanosomes occur in tandem and that the rates of both are higher in these cells than in melanocytes of normally pigmented control chickens. Assays for tyrosinase activity in feather follicles indicate a hypermelanization in eDAM feathers and in the pigmented feathers of young Smyth chicks prior to the onset of depigmentation. Finally, we report on the establishment of pure, proliferative cultures of neural crest-derived melanocytes from control and Smyth chicken embryos. The degenerative events in Smyth chicken melanocyte cultures mimic in part those of the cells in vivo and are therefore indicative of a genetic defect that is independent of the immune system.