Novel phenotype in beagle dogs characterized by skin response to compound 48/80 focusing on skin mast cell degranulation

Abstract

Beagle dogs have long been employed in toxicology studies and as skin disease models. Compared with other experimental animal species, they are known to be susceptible to skin responses, such as rashes, from exposure to various chemical compounds. Here, a unique dog phenotype was identified that showed no skin response to compound 48/80, a mast cell degranulating agent. Although the skin responses to intradermal injection of polyoxyethylene castor oil derivative (HCO-60, a nonionic detergent), histamine dihydrochloride, concanavalin A (IgE receptor-mediated stimuli), or calcium ionophore A23187 were comparable in wild-type (WT) dogs and these nonresponder (NR) dogs, only the response to compound 48/80 was entirely absent from NR dogs. The skin mast cell density and histamine content per mast cell were histologically comparable between WT and NR dogs. By checking for skin responses to compound 48/80, NR dogs were found to exist at the proportion of 17–20% among four animal breeders. From retrospective analysis of in-house breeding histories, the NR phenotype appears to conform to the Mendelian pattern of recessive inheritance. The standard skin response in WT dogs developed at 2–4 months of age. In conclusion, this unique phenotype, typified by insensitivity in the compound 48/80-induced degranulation pathway in mast cells, has been widely retained by recessive inheritance in beagle dogs among general experimental animal breeders. The knowledge concerning this phenotype could lead to better utilization of dogs in studies and aid in model development.

Cutaneous anaphylactoid reaction to polyoxyethylene hydrogenated castor oil in dogs

“…29,30 It has been reported that in a unique nonresponsive phenotype of compound 48/80 in beagle dogs, compound 48/80 did not induce anaphylactoid skin reaction as per IDT, while HCO-60 did. 31 The significant difference in IDT score and percentage of mast cell degranulation within the dog groups in the present study indicate there is the possibility that individual differences in the response of HCO-ethoxylate could be present. Individual differences might be one reason why we experienced the uncommon anaphylactoid reaction to an ear drop.…”

“…Compound 48/80 is a potent chemical inducer of mast cell degranulation, and it has been shown to relay the signalling leading to mast cell degranulation via binding to mas‐related G protein‐coupled‐receptor X2 (MRGPRX2) in humans or MRGPRB2 in mice 29,30 . It has been reported that in a unique nonresponsive phenotype of compound 48/80 in beagle dogs, compound 48/80 did not induce anaphylactoid skin reaction as per IDT, while HCO‐60 did 31 . The significant difference in IDT score and percentage of mast cell degranulation within the dog groups in the present study indicate there is the possibility that individual differences in the response of HCO‐ethoxylate could be present.…”

Preclinical species gene expression database: Development and meta-analysis

“…Our effort found 19,856 protein coding and 4,724 non-protein coding genes in beagle dogs ( Table 2 ). This work was conducted in the dog strain (Beagle) used for drug safety toxicology studies ( Weber et al, 2011 ; Uchida et al, 2015 ). At the time of this publication, the only dog related RNAseq databases that exist are focused on tumor tissue.…”