Human Hereditary Sensory Autonomic Neuropathies (HSANs) are characterized by insensitivity to pain, sometimes combined with self-mutilation. Strikingly, several sporting dog breeds are particularly affected by such neuropathies. Clinical signs appear in young puppies and consist of acral analgesia, with or without sudden intense licking, biting and severe self-mutilation of the feet, whereas proprioception, motor abilities and spinal reflexes remain intact. Through a Genome Wide Association Study (GWAS) with 24 affected and 30 unaffected sporting dogs using the Canine HD 170K SNP array (Illumina), we identified a 1.8 Mb homozygous locus on canine chromosome 4 (adj. p-val = 2.5x10^-6). Targeted high-throughput sequencing of this locus in 4 affected and 4 unaffected dogs identified 478 variants. Only one variant perfectly segregated with the expected recessive inheritance in 300 sporting dogs of known clinical status, while it was never present in 900 unaffected dogs from 130 other breeds. This variant, located 90 kb upstream of the GDNF gene, a highly relevant neurotrophic factor candidate gene, lies in a long intergenic non-coding RNAs (lincRNA), GDNF-AS. Using human comparative genomic analysis, we observed that the canine variant maps onto an enhancer element. Quantitative RT-PCR of dorsal root ganglia RNAs of affected dogs showed a significant decrease of both GDNF mRNA and GDNF-AS expression levels (respectively 60% and 80%), as compared to unaffected dogs. We thus performed gel shift assays (EMSA) that reveal that the canine variant significantly alters the binding of regulatory elements. Altogether, these results allowed the identification in dogs of GDNF as a relevant candidate for human HSAN and insensitivity to pain, but also shed light on the regulation of GDNF transcription. Finally, such results allow proposing these sporting dog breeds as natural models for clinical trials with a double benefit for human and veterinary medicine. In this study, we present a canine neuropathy characterized by insensitivity to pain in the feet, sometimes combined with self-mutilation described in four sporting breeds. This particular phenotype has the clinical hallmarks of human Hereditary Sensory Autonomic Neuropathies (HSAN). As we hypothesized that a monogenic recessive disorder was shared between these breeds, we performed a Genome Wide Association Study (GWAS) to search for the genetic causes and found one homozygous chromosomal region in affected dogs. High-throughput sequencing of this region allowed the identification of a point mutation upstream to the GDNF gene and located in the last exon of a long non-coding RNA, GDNF-AS. We confirmed the perfect association of this variant with the disease using more than 900 unaffected dogs that do not present with this mutation. Functional analyses (qRT-PCR, EMSA) confirmed that the mutation alters the binding of regulatory complex, leading to a significant decrease of both GDNF and GDNF-AS mRNA expression levels. This work in canine spontaneous forms of human neuropathies allowed the identification of a novel gene GDNF and its regulation mechanism, not yet described in human HSAN, opening the field of clinical trials to benefit both canine and human medicine.

Quantitative data on fecal shedding of antimicrobial-resistant bacteria are crucial to assess the risk of transmission from dogs to humans. Our first objective was to investigate the prevalence of quinolone/fluoroquinolone-resistant and beta-lactam-resistant Enterobacteriaceae in dogs in France and Spain. Due to the particular concern about possible transmission of extended-spectrum cephalosporin (ESC)-resistant isolates from dogs to their owners, we characterized the ESBL/pAmpC producers collected from dogs. Rectal swabs from 188 dogs, without signs of diarrhea and that had not received antimicrobials for 4 weeks before the study, were quantified for total and resistant Enterobacteriaceae on selective media alone or containing relevant antibiotic concentrations. Information that might explain antibiotic resistance was collected for each dog. Extended-spectrum cephalosporin-resistant isolates were subjected to bacterial species identification (API20E), genetic lineage characterization (MLST), ESBL/pAmpC genes identification (sequencing), and plasmid characterization (pMLST). Regarding beta-lactam resistance, amoxicillin- (AMX) and cefotaxime- (CTX) resistant Enterobacteriaceae were detected in 70 and 18% of the dogs, respectively, whereas for quinolone/fluoroquinolone-resistance, Nalidixic acid- (NAL) and ciprofloxacin- (CIP) resistant Enterobacteriaceae were detected in 36 and 18% of the dogs, respectively. Medical rather than preventive consultation was a risk marker for the presence of NAL and CIP resistance. CTX resistance was mainly due to a combination of specific ESBL/pAmpC genes and particular conjugative plasmids already identified in human patients: bla_CTX−M−1/IncI1/ST3 (n = 4), bla_CMY−2/IncI1/ST12 (n = 2), and bla_CTX−M−15/IncI1/ST31 (n = 1). bla_SHV−12 (n = 3) was detected in various plasmid lineages (InI1/ST3, IncI1/ST26, and IncFII). ESBL/pAmpC plasmids were located in different genetic lineages of E. coli, with the exception of two strains in France (ST6998) and two in Spain (ST602). Our study highlights dogs as a potential source of Q/FQ-resistant and ESBL/pAmpC-producing bacteria that might further disseminate to humans, and notably a serious risk of future acquisition of CTX-M-1 and CMY-2 plasmids by the owners of dogs.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for COVID-19 in people, has been detected in companion animals on rare occasions. A limited number of large-scale studies have investigated the exposure of companion animals to SARS-CoV-2. The objective of this prospective study was to estimate seroprevalence in privately owned dogs and cats presented in veterinary clinics in different French regions and to test the hypothesis that the occurrence of an episode of COVID-19 in the household and close contact with the owner would increase the chances of the animals being seropositive. One hundred and sixty-five dogs and 143 cats were blood-sampled between March 2020 and December 2021. Neutralizing SARS-CoV-2 antibodies were detected in 8.4% of cats (12/143) and 5.4% of dogs (9/165). Seven animals (three dogs and four cats) were seropositive in the absence of an episode of COVID-19 in the household. Despite not being statistically significant (chi-square test, p-value = 0.55), our data may suggest that the occurrence of an episode of COVID-19 in the household could increase the risk of animal seropositivity (odds ratio = 1.38; 95% confidence interval = 0.55–3.77). This survey indirectly shows that SARS-CoV-2 circulates in canine and feline populations, but its circulation appears to be too low for pets to act as a significant viral reservoir.

Canine haircoat quality, the time course of incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into the canine erythrocyte membrane, changes in total lipids content on hair shafts and of neutral lipids on the skin surface, were investigated after administrating an n-3 fatty acids supplement. Twenty-four dogs with poor haircoat received a placebo or n-3 oil capsules (110 mg EPA/68 mg DHA) daily for 90 days. Clinical assessments and tissue sampling were performed monthly from day (D)0 to D180. The clinical score in treated dogs was significantly reduced from D60, then attained a plateau and returned to baseline levels on D180. EPA and DHA contents in the erythrocyte membrane increased significantly from D30 and decreased rapidly after supplement withdrawal in treated dogs. Total lipids on the hair shaft increased progressively in the supplemented group. EPA/DHA supplements impact blood and hair fatty acids important for haircoat quality in dogs.