Independent DSG4 frameshift variants in cats with hair shaft dystrophy.

Investigations of hereditary phenotypes in spontaneous mutants may help to better understand the physiological functions of the altered genes. We investigated two unrelated domestic shorthair cats with bulbous swellings of the hair shafts. The clinical, histopathological, and ultrastructural features were similar to those in mice with lanceolate hair phenotype caused by loss-of-function variants in Dsg4 encoding desmoglein 4. We sequenced the genomes from both affected cats and compared the data of each affected cat to 61 control genomes. A search for private homozygous variants in the DSG4 candidate gene revealed independent frameshift variants in each case, c.76del or p.Ile26fsLeu*4 in case no. 1 and c.1777del or p.His593Thrfs*23 in case no. 2. DSG4 is a transmembrane glycoprotein located primarily in the extracellular part of desmosomes, a complex of adhesion molecules responsible for connecting the keratin intermediate filaments of neighbouring epithelial cells. Desmosomes are essential for normal hair shaft formation. Both identified DSG4 variants in the affected cats lead to premature stop codons and truncate major parts of the open-reading frame. We assume that this leads to a complete loss of DSG4 function, resulting in an incorrect formation of the desmosomes and causing the development of defective hair shafts. Together with the knowledge on the effects of DSG4 variants in other species, our data suggest that the identified DSG4 variants cause the hair shaft dystrophy. To the best of our knowledge, this study represents the first report of pathogenic DSG4 variants in domestic animals.

The creation of an assessment tool for the analysis of two forms of heat damage in animal hair.

Animal cruelty cases can involve a variety of mistreatment to domestic animals. A common source of abuse is the use of heat sources, such as ovens, hot surfaces and microwaves. Analysis of damage to skin by a veterinarian is a key aspect of these investigations but additional information can be provided by observing the hair of the animal, including heat source type and exposure time. This study developed an objective grading system for the analysis of heat damage in hairs which can be used to quantify different damage characteristics including bubbling, discolouration, expansion of hair, fractures, changes to the medulla and scales and scale removal/melting. This grading scheme was applied to the investigation of dog (Canis familiaris) skin samples with full pelage and loose hairs exposed to microwaves and a heated environment in order to identify any distinguishing damage characteristics from the two different heated environments. Samples were exposed to a furnace for 1min at different temperature ranges (50-350°C with 50°C intervals) and also a microwave at maximum power for different time periods (15, 30, 45, 60, 120, 180, 240 and 300s). Hairs were extracted for examination using high powered light microscopy and scanning electron microscopy. Overall, it can be determined that the type of damage observed is influenced by the nature of heat applied and the context and substrate in which the hair is situated at the time of exposure. Using principal component analysis (PCA) it was concluded that as temperature increases in a furnace so does the severity of each of the damage characteristics observed. It can be noted that with furnace exposure, any one of the characteristics could be used to indicate the temperature to which it has been exposed. For furnace exposed samples there was no significant difference between loose or embedded hairs. PCA analysis determined that there are two independent forms of damage that occur when hairs are exposed to microwave radiation, these are: increased bubbling and discolouration in the root and increased bubbling and discolouration of the shaft and tip. Exposure time is correlated with both the root and shaft/tip observations. The results indicated some clear distinctions between heat source and exposure useful for the objective interpretation of such evidence. This standardised approach for the observation of heat damage characteristics in animal hair provides investigators with a tool to differentiate between methods of abuse, providing a greater understanding of the crime committed.

Extending the Mathematical Palette for Developmental Pattern Formation: Piebaldism.

Here, we present a theoretical investigation with potential insights on developmental mechanisms. Three biological factors, consisting of two diffusing factors and a cell-autonomous immobile transcription factor are combined with different feedback mechanisms. This results in four different situations or fur patterns. Two of them reproduce classical Turing patterns: (1) regularly spaced spots, (2) labyrinth patterns or straight lines with an initial slope in the activation of the transcription factor. The third situation does not lead to patterns, but results in different homogeneous color tones. Finally, the fourth one sheds new light on the possible mechanisms leading to the formation of piebald patterns exemplified by the random patterns on the fur of some cows' strains and Dalmatian dogs. Piebaldism is usually manifested as white areas of fur, hair, or skin due to the absence of pigment-producing cells in those regions. The distribution of the white and colored zones does not reflect the classical Turing patterns. We demonstrate that these piebald patterns are of transient nature, developing from random initial conditions and relying on a system's bistability. We show numerically that the presence of a cell-autonomous factor not only expands the range of reaction diffusion parameters in which a pattern may arise, but also extends the pattern-forming abilities of the reaction-diffusion equations.

Description and characterization of a hair coat disorder in schipperkes.

BACKGROUND: Schipperkes develop bilaterally symmetrical alopecia preceded by lightening of the hair coat not associated with systemic clinical signs. The alopecia is presumptively diagnosed as Alopecia X but has never been investigated. HYPOTHESIS/OBJECTIVES: The purpose of this study was to describe clinical features, histopathological and laboratory abnormalities associated with symmetrical, noninflammatory alopecia in schipperkes. ANIMALS: Three healthy and eight affected schipperkes. METHODS AND MATERIALS: Complete blood count (CBC), serum chemistry panel, urinalysis (UA), urine cortisol: creatinine ratio (UCCR), total thyroxine (T4 ), free thyroxine by equilibrium dialysis (fT4 ed), thyroid stimulating hormone (TSH) and pre- and post-stimulation cortisol with sex hormone analyses were performed for all dogs. A minimum of two skin biopsy sites were sampled for histopathological evaluation. RESULTS: The CBC, serum chemistry panel, UA, T4 , fT4 ed, TSH and post-ACTH cortisol concentrations were normal for all dogs. Androstenedione concentrations were increased for all dogs; two of three healthy and five of eight affected dogs had increased post-ACTH androstenedione concentrations. Estradiol concentrations were increased for all healthy and four of eight affected dogs, with post-ACTH estradiol concentrations increased for all healthy and five of eight affected dogs. Progesterone concentrations were increased for two of three healthy and four of eight affected dogs. Post-ACTH progesterone concentrations were increased for one of three healthy and four of eight affected dogs. For one of three healthy and two of eight affected dogs, 17-hydroxyprogesterone concentrations were increased; post-ACTH 17-hydroxyprogesterone concentrations were increased in three of eight affected dogs only. Histopathology results from affected dogs were consistent with hair cycle arrest. CONCLUSIONS AND CLINICAL IMPORTANCE: This disorder resembles Alopecia X clinically and histologically.

Timing and Appearance of Postmortem Root Banding in Nonhuman Mammals.

A study was undertaken using nonhuman mammal specimens to better understand environmental influences on postmortem hair root band (PMRB) formation and to see whether PMRBs would occur in nonhuman mammal hairs in a similar fashion to human hairs. Carcasses from surrounding roadways were the primary source of specimens for this study, augmented by donated deceased domestic pets. Sections of pelt from each specimen were placed in controlled environmental conditions while the remainder of the carcass was left in a secure outdoor setting. Hair samples were collected daily from outdoor and control specimens and examined for evidence of PMRBs. Several environmental factors were also recorded on a daily basis. Results demonstrate PMRBs can occur in nonhuman mammal hairs, and they have microscopic characteristics similar to human PMRBs. Factors found to correlate with PMRB formation include postmortem interval, temperature, pH, and the formation and subsequent volatilization of ammonia from the surrounding tissue.

A valid method to determine the site of drowning.

The diatom test is considered a useful aid in determining the site of death from drowning. Nevertheless, there is disagreement within the scientific community concerning its reliability, and its findings have been challenged and sometimes overturned in courts of law. Using a model based on animal experimentation, we have developed a diatom test to discriminate between the locations of drowning sites from different aquatic systems. We carried out a complementary combination of quantitative and qualitative analyses together with a statistical analysis based on the Kullback-Leibler distance of the samples. A restrictive selection of exclusive diatom species from each reservoir was also made. This approach allowed us to validate the usefulness of the diatom test in determining the location of the site of drowning.