Ichthyosis fetalis in Polled Hereford and Shorthorn calves
Inherited forms of ichthyosis, or generalized scaling of the skin, have been reported in many animal species, including cattle, and are characterized by an autosomal recessive mode of inheritance. We investigated 2 calves affected with ichthyosis fetalis, a Polled Hereford and a Shorthorn. Both cases had hard white plaques on the skin consistent with excessive keratinization. This was confirmed by histopathology, which showed severe diffuse epidermal and follicular orthokeratotic hyperkeratosis. The known mutation (H1935R) in gene ABCA12, responsible for ichthyosis fetalis in Chianina cattle, was shown to be absent in both affected calves and their obligate heterozygous parents. These molecular findings indicate that allelic heterogeneity exists for this condition in cattle.
Molecular basis of a new ovine model for human 3M syndrome-2
Background Brachygnathia, cardiomegaly and renal hypoplasia syndrome (BCRHS, OMIA 001595–9940 ) is a previously reported recessively inherited disorder in Australian Poll Merino/Merino sheep. Affected lambs are stillborn with various congenital defects as reflected in the name of the disease, as well as short stature, a short and broad cranium, a small thoracic cavity, thin ribs and brachysternum. The BCRHS phenotype shows similarity to certain human short stature syndromes, in particular the human 3M syndrome-2. Here we report the identification of a likely disease-causing variant and propose an ovine model for human 3M syndrome-2. Results Eight positional candidate genes were identified among the 39 genes in the approximately 1 Mb interval to which the disease was mapped previously. Obscurin like cytoskeletal adaptor 1 ( OBSL1 ) was selected as a strong positional candidate gene based on gene function and the resulting phenotypes observed in humans with mutations in this gene. Whole genome sequencing of an affected lamb (BCRHS3) identified a likely causal variant ENSOARG00000020239:g.220472248delC within OBSL1 . Sanger sequencing of seven affected, six obligate carrier, two phenotypically unaffected animals from the original flock and one unrelated control animal validated the variant. A genotyping assay was developed to genotype 583 animals from the original flock, giving an estimated allele frequency of 5%. Conclusions The identification of a likely disease-causing variant resulting in a frameshift (p.(Val573Trpfs*119)) in the OBSL1 protein has enabled improved breeding management of the implicated flock. The opportunity for an ovine model for human 3M syndrome and ensuing therapeutic research is promising given the availability of carrier ram semen for BCRHS.
Photosensitization Outbreak in Shorthorn Calves in Missouri
Photosensitization (PS) occurred in Shorthorn calves from 3 herds in Boone County, Missouri, in late August and early September 1989. In herd 1, 3 calves, 3-4 weeks old, from a herd of 35 cows with calves were mildly photosensitized. The cattle were confined to 37 acres of permanent pasture of mixed grass and red clover undersown in the previous year’s wheat crop. Skin lesions were most conspicuous on sparsely haired areas around the face and ears. According to the owner, these calves had avoided exposure to full sun for the previous 2 weeks. Two of the calves had slightly elevated gamma glutamyl transferase (GGT) activity. Other evidence of mild liver damage was indicated by a slight elevation in bilirubin (Table 1). These calves recovered during the next week. In herd 2, the 8 affected calves were 2-3 weeks old. The calves and dams were kept in a 4-acre pasture of fescue and red clover. On September 1, the owner noticed flaking skin and hair loss on the backs of the ears of several calves. More calves were affected the next day, and hair loss along the dorsal midline was evident. All calves were photophobic, and 6 of the 8 had diarrhea. At clinical examination on September 6, all 8 calves had lesions evident at various locations (8/8 ears, 6/8 head, 5/8 withers, 4/8 back, and 2/8 dewlap). Other signs of moderate PS included lacrimation, erythema, cutaneous edema, fissuring of the epithelium, and scattered crusting of serum on nonpigmented exposed skin. Serum values for aspartate aminotransferase (AST) were within the normal range. Elevated GGT activity was compatible with damage to the biliary tree. Recovery occurred during the next 3 weeks. Photosensitization is the development of hyperreactivity of the skin to sunlight. The photoreactive molecule, synonymous with photosensitizer, functions as an energy transducer to convert light energy into molecular electronic energy in the form of activated chemical species. Specific biochemical and functional effects of PS reactions include formation of photoadducts with DNA and proteins, peroxidation of lipids, photo-oxidation of membrane proteins, inhibition of transport of essential metabolites, and leakage of lysosomal enzymes. Irrespective of the cause, clinical PS resembles a severe sunburn. The progressive clinical manifestation of PS consists of lacrimation, photophobia, erythema, cutaneous edema, fissuring of the epithelium, exudation and crusting of serum, and necrosis and sloughing of nonpigmented exposed skin Corneal edema is also evident in many cases. Additional clinical signs consistent with liver damage commonly seen in secondary PS include icterus, anorexia, and depression.