Efficacy of hydroquinone in the treatment of cutaneous hyperpigmentation in hairless descendants of Mexican hairless dogs (Xoloitzcuintli)

The skin of adult hairless dogs is clinically nonpigmented, clinically lightly pigmented, or clinically hyperpigmented (spotty pigmented). The pigment noted clinically is attributable to melanin granules in the epidermis. Spotty pigmentation in the skin of adult hairless dogs was treated by administration of the depigmenting agent (3% hydroquinone, HQ) for 1 month. Depigmenting effects were examined by use of three methods: skin color, dihydroxyphenylalanine (DOPA)-positive melanocyte count, and histologic evaluation. The treated skin of hairless dogs began to become depigmented after application of HQ for 1 week. After 1 month of treatment with HQ, depigmentation spread over a quarter of the body. The number of DOPA-positive melanocytes in the HQ-treated sites decreased to less than approximately a fifth of that before treatment. In HQ-treated skin, histologic staining by use of Fontana-Masson's (FM) method revealed complete absence of melanin pigment. These results suggested that hairless dogs should be a useful animal model for investigating the effects and cutaneous toxicity of depigmenting agents.     

Characteristics of a new hairless mutation (bald) in rats

Hereditarily hairless rats have been maintained by sibmatings since 1973. These animals were termed "bald rats", and examined for their characteristics on genetics, physiological, hematological and clinical chemistry values and histology. The bald rats began to lose their hair at approximately three weeks of age. At five weeks of age, the skin was devoid of all general body hair except for the vibrissae, and the skin became wrinkled at two months of age. Histologically, follicular cysts were observed in a large number, from three months of age onward. The bald condition was a simple recessive character (ba); homozygous animals lost hair and heterozygous ones did not. The bald females attained sexual maturity around eight weeks of age and littered normally, but failed to nurse their young. The incapability of supplying sufficient milk supposedly resulted from the mammary glands that involuted after delivery. The bald animals consumed more food but showed lower values for body weights, plasma triglyceride, and epididymal adipose tissue amount than the haired animals. In addition, the bald males had brown adipose tissue in the interscapulum which was histologically activated as in newborn animals. Aged bald animals showed spontaneous tumors of the thymus, pituitary, testis, uterus, mammary gland, and skin. The incidence of skin tumors was much higher than those of tumors of other origins.     

Intragenic deletion in the Desmoglein 4 gene underlies the skin phenotype in the Iffa Credo "hairless" rat

The Iffa Credo (IC) "hairless" rat is an autosomal recessive hypotrichotic animal model actively used in pharmacological and dermatological studies. Although the molecular basis of the IC rat phenotype was never defined, the designation "hr/hr" (hairless) has been used for this rat mutation. Despite the observation that IC rats share many phenotypic similarities with Charles River (CR) 'hairless rats', crossbreeding between CR and IC rats indicated that these mutations are not allelic, and moreover, genetic analysis of both CR and IC hairless mutant rats showed no mutations in the hr gene. Here, we present a detailed analysis of the skin phenotype in the IC rat. While the initial stages of hair follicle (HF) morphogenesis reveal no significant abnormalities, the subsequent processes of inner root sheath and hair shaft formation are severely disturbed due to impaired proliferation in the hair matrix and abnormal differentiation in the precortex zone. This results in significant reduction of hair bulb volume, and the formation of dysmorphic "blebbed" hair shafts lacking medullar structure and resembling "lanceolate" hairs. Based on the presence of lance-head hairs typical of rodent lanceolate mutants, we performed molecular analysis of the desmoglein 4 gene and found a large intragenic deletion encompassing nine exons of the gene. This finding, together with specific morphological features of skin and hairs, confirms that the IC rat is allelic with the lanceolate hair (lah) mutations in mice and rats. Our results elucidate the genetic and morphological basis of the IC rat mutation, thus providing a new model to study molecular mechanisms of hair growth control.     

Morphology of germ-free piglets

The postnatal ontogeny of primary (thymus) and secondary (spleen, lymph node, lingual tonsil) lymphoid tissues was studied in germ-free colostrum-deprived piglets up to age of 68 days. The thymus, which is morphologically fully developed by the end of gestation, showed no significant differences in the germ-free and conventional state. In germ-free piglets, slow development of periarteriolarly organized lymph follicles occurred in the spleen up to the end of the observation period. As distinct from the conditions in the spleen of conventional animals, the presence of a large number of pyroninophilic cells was not observed in germ-free piglets and no germinal centres were found. A similar situation was seen in the mesenteric lymph nodes, in which, in conventional piglets, cells belonging to the plasmacyte series, as well as the germinal centres, proliferate by the 13th day. Differences were also found in the organization of the follicular lymphoid tissue in the wall of the terminal ileum. In germ-free piglets, the lymph follicles increased only very slowly in size during the observation period and germinal centres were absent, while in conventional piglots germinal centres were present from the 12th day. The view is expressed that the intestinal lymphoid tissue ought rather to be classified as peripheral lymphoid tissue.     

Lymphoid organ weights and organ:body weight ratios of growing beagles

Although dogs, especially beagles, are used extensively in biological and clinical investigations, the literature dealing with normal biological measurements of their lymphoid organs is scanty. This study was undertaken to provide the information on the weight of lymphoid organs of beagles. The thymus, spleen, and prescapular, popliteal, and mesenteric lymph nodes of 95 normal beagle dogs, from one day to 11 months of age, were weighed and compared with body weights. The weight of the thymus and spleen increased drastically at and after 2 months of age, although the organ:body weight ratios remained the same at 2 months of age and decreased afterward. Similar increases in the weight of the mesenteric lymph node complex, but with an increase in the organ:body weight ratio, occurred also at and after 2 months of age, reflecting the importance of the gut-associated lymphoid organs after weaning. The increases in the size of the cutaneous nodes, prescapular and popliteal, were less pronounced and their organ:body weight ratios remained the same from birth through 11 months of age.     

Maintenance of distinct melanocyte populations in the interfollicular epidermis

Hair follicles and sweat glands are recognized as reservoirs of melanocyte stem cells (MSCs). Unlike differentiated melanocytes, undifferentiated MSCs do not produce melanin. They serve as a source of differentiated melanocytes for the hair follicle and contribute to the interfollicular epidermis upon wounding, exposure to ultraviolet irradiation or in remission from vitiligo, where repigmentation often spreads outwards from the hair follicles. It is unknown whether these observations reflect the normal homoeostatic mechanism of melanocyte renewal or whether unperturbed interfollicular epidermis can maintain a melanocyte population that is independent of the skin's appendages. Here, we show that mouse tail skin lacking appendages does maintain a stable melanocyte number, including a low frequency of amelanotic melanocytes, into adult life. Furthermore, we show that actively cycling differentiated melanocytes are present in postnatal skin, indicating that amelanotic melanocytes are not uniquely relied on for melanocyte homoeostasis.     

Postnatal development of the skin of the marsupial native cat Dasyurus hallucatus

Skin development of the Northern native cat was examined from birth to weaning at 150 days post partum. An outer layer of cells, termed the periderm or epitrichium, is present on the epidermis of the newborn. This layer of cells is not discernible at 7 days post partum. Skin development of the native cat differs from that of the eutherian mammal. The periderm of the eutherian is no longer discernible when the developing hairs first penetrate the epidermis. In the marsupial, this loss of the periderm occurs well before the appearance of follicles. Melanocytes and Langerhans cells are seen at day 23 post partum, follicles at day 30, sebaceous glands at day 59, and sweat glands at day 67. Thus, when the mother first leaves her young in the nest at about days 60 to 70 of lactation, the skin is at a stage of development that will assist the young with thermoregulation. The skin continues to develop throughout lactation and attains an adult appearance by day 150 post partum.     

Sostdc1 defines the size and number of skin appendage placodes

Mammary glands and hair follicles develop as ectodermal organs sharing common features during embryonic morphogenesis. The molecular signals controlling the initiation and patterning of skin appendages involve the bone morphogenetic proteins and Wnt family members, which are commonly thought to serve as inhibitory and activating cues, respectively. Here, we have examined the role of the Bmp and Wnt pathway modulator Sostdc1 in mammary gland, and hair and vibrissa follicle development using Sostdc1-null mice. Contrary to previous speculations, loss of Sostdc1 did not affect pelage hair cycling. Instead, we found that Sostdc1 limits the number of developing vibrissae and other muzzle hair follicles, and the size of primary hair placodes. Sostdc1 controls also the size and shape of mammary buds. Furthermore, Sostdc1 is essential for suppression of hair follicle fate in the normally hairless nipple epidermis, but its loss also promotes the appearance of supernumerary nipple-like protrusions. Our data suggest that functions of Sostdc1 can be largely attributed to its ability to attenuate Wnt/β-catenin signaling.     

Analysis of the effects of mutant hairless genes in chimeric mice

The autosomal recessive gene hairless (hr) is responsible for the complete hairlessness in mice homozygous for this gene. Hair shedding that begins at the age of 10 days is caused by an abnormal cycle of hair follicle development disturbed at the catagen stage. This results in enhanced programmed cell death (apoptosis) and ultimately leads to the complete hair follicle destruction and shedding of all hairs by the age of three weeks. To study the phenotypic expression of the hr gene in a chimeric organism, we have obtained 12 chimeric mice hr/hr <--> +/+ by means of aggregation of early embryos hr/hr and +/+. In chimeric mice, the hair shedding has begun two days later than in the hr/hr mice. By day 23 of postnatal development, hairless areas were present on the coat of chimeric mice or the latter were completely hairless depending on the percentage of the hr/hr mutant component. In four chimeras with high content of the mutant component (68-76%), the hair shedding process was similar to that in the hr/hr mice, though it was accomplished two days later. In three chimeras with 48-51% of the mutant component, alternating hairless and hair-covered bands were observed. These data suggest that the hr gene acts in epidermal cells of a hair follicle, because epidermal cell clones in embryonic skin migrate in the lateral-ventral direction coherently and without mixing. However, some chimeras displayed a pattern which was not so clear-cut: the band borders were illegible and hairs partly covered the hairless areas. In some chimeras, the uniform thinning of the coat was observed. Analysis of the effects of the hr mutant gene in chimeric mice differing in the ratio between mutant (hr/hr) and normal (+/+) components in tissues suggests that the hr gene acts in the epidermal cells of the hair follicle. The interactions between cells have an essential effect on the mode and degree of the hr gene expression, which leads to distortion of the "ectodermal" coat pattern in chimeras.     

Immunohistochemical comparison of whisker pad cutaneous innervation in Swiss Webster and hairless mice

To establish the mouse mutant, hairless (Hr), as a useful model for future analyses of target-ending interactions, we assessed the cutaneous innervation in the whisker pad after loss of primary hair targets. Postnatal (P) development of fur in Hr begins similarly to that of "normal" Swiss Webster (SW) mice. Around P10, hairs are shed and the follicles rendered permanently incompetent. Hair loss progresses rostrocaudally until the entire skin is denuded. Substantial alterations in the distribution and density of sensory and autonomic endings in the mystacial pad vibrissal and intervibrissal fur innervation were discovered. Pilo-neural complexes innervating fur hairs were dismantled in Hr. Epidermal innervation in SW was rich; only a few endings expressed growth-associated protein-43?kdal (GAP), suggesting limited changes in axonal elongation. Innervation in Hr formed a dense layer passing upward through the thickened epidermis, with substantial increases among all types of endings. Vibrissal follicle-sinus complexes were also hyperinnervated. Endings in Hr vibrissae and fur were strongly GAP-positive, suggesting reorganization of innervation. Dermal and vascular autonomic innervation in both strains co-localized tyrosine hydroxylase and neuropeptide Y, but only in Hr did neuropeptide Y co-localize calcitonin gene-related peptide (CGRP) and express GAP immunolabeling. Stereological quantitation of trigeminal ganglia revealed no differences in neuron number between Hr and SW, although there were small increases in cell volume in Hr trigeminal ganglion cells. These results suggested that a form of collateral sprouting was active in Hr mystacial pads, not in response to local injury, but as a result of loss of primary target tissues.     

The cutaneous microbiology of haired and hairless mice

H arnby , D., G owland , G., H olland , K.T. & K earney , J.N. 1990. The cutaneous microbiology of haired and hairless mice. Journal of Applied Bacteriology 69 , 686–691.
The cutaneous microflora of the mid-dorsal area of hairless and haired mice was studied by processing skin biopsies. In both C3H and CBA hairless genotype animals the prevalence of colonization and the bacterial density were significantly greater than in the haired animals. The dominant bacteria were staphylococci and aerobic coryneforms. No propionibacteria were isolated. Temporal studies with C3H mice showed that from 0 to 9 days after birth the cutaneous microflora reduced and from then on the haired genotype animals maintained a low cutaneous microflora, whilst hairless genotype animals gradually lost hair from head to tail and the microflora density increased. Reciprocal skin grafting between haired and hairless animals showed that the donor skin acquired the microflora characteristics of the recipient animal after 15 d post-grafting even though the donor skin remained morphologically true to genotype.     

Profile of hematological values in hybrid hairless dogs

The purpose of this paper is to describe some fundamental physiological data in F 1 hybrids bred from a Mexican hairless dog and beagle cross. These F 1 hybrids numbered 5 hairless dogs and 12 haired dogs. The hematological profile of these offspring was assessed via an automated cell counter and compared with those of healthy beagles. In hairless dogs, red blood cell count, hemoglobin concentration and packed cell volume tended to be higher than in beagles. White cell distribution curves in hairless dogs and beagles yielded a single peak, while in haired dogs one or two peaks were present. Red blood cell and platelet distribution curves revealed few differences among the 3 kinds of dogs.     

A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning

To understand the role Fgf signalling in skin and hair follicle development, we analysed the phenotype of mice deficient for Fgfr2-IIIb and its main ligand Fgf10. These studies showed that the severe epidermal hypoplasia found in mice null for Fgfr2-IIIb is caused by a lack of the basal cell proliferation that normally results in a stratified epidermis. Although at term the epidermis of Fgfr2-IIIb null mice is only two to three cells thick, it expresses the classical markers of epidermal differentiation and establishes a functional barrier. Mice deficient for Fgf10 display a similar but less severe epidermal hypoplasia. By contrast, Fgfr2-IIIb-/-, but not Fgf10-/-, mice produced significantly fewer hair follicles, and their follicles were developmentally retarded. Following transplantation onto nude mice, grafts of Fgfr2-IIIb-/- skin showed impaired hair formation, with a decrease in hair density and the production of abnormal pelage hairs. Expression of Lef1, Shh and Bmp4 in the developing hair follicles of Fgfr2-IIIb-/- mice was similar to wild type. These results suggest that Fgf signalling positively regulates the number of keratinocytes needed to form a normal stratified epidermis and to initiate hair placode formation. In addition, Fgf signals are required for the growth and patterning of pelage hairs.     

A histological study on the skin and hairs of PC (poor coat) mice

Light microscopic examinations were done on the skin and hairs of PC (poor coat) mice, maintained as an inbred strain at the National Institute of Health, Japan. The structures of the epidermis, dermis, hair root sheath and the sebaceous glands were normal. Hair bulbs and hair papillae were poorly developed at anagen stage of hair cycle. Having scanty medulla, the hairs were thin and short. The hair cuticle appeared normal. These findings suggest that the defective hair growth in PC mice is caused by deficiencies in cell differentiation and/or proliferation in the hair matrix.