Hypothyroidism in a dog associated with trimethoprimsulphadiazine therapy

Abstract Hypothyroidism and a neuromuscular disorder developed in a 4-year-old Golden Retriever after it received potentiated sulphonamide and metronidazole for 18 and 14 weeks, respectively. Serum total T4 concentrations were non-detectable before and 6 h after exogenous administration of 4IU bovine thyroidstimulating hormone. Thyroid gland biopsy revealed changes consistent with diffuse hyperplastic goitre. Serum T4 concentrations were normal 7 days after discontinuation of therapy. The long-term trimethoprim-sulphadiazine therapy was considered the most likely cause of this dog's hyperplastic goitre. The cause of the neuromuscular disorder was not determined. It is recommended that discontinuation of potentiated sulphonamide takes place at least 7 days prior to any assessment of thyroid function. Résumé— Une hypothyroïdie et des troubles neuromusculaires sont observés sur un Golden Retriever de 4 ans, après une thérapeutique à base de sulfonamides potentialisés et de métronidazole, respectivement de 18 et 14 semaines. Des concentrations sériques de T4 totale ne sont pas détectables avant et après 6 heures d'une stimulation à la TSH bovine (4 UI). Des biopsies de la thyroïde montrent un goitre hyperplasique diffus. Les concentrations sériques de T4 sont de nouveau normales 7 jours après l'arrêt du traitement. L'administration à long terme de triméthoprim-sulphadiazine semble être la cause la plus vraisemblable du goitre hyperplasique. La cause des troubles neuromusculaires n'a pas été déterminée. Il est recommandé d'arrêter l'administration de sulfonamides potentialisés au moins 7 jours avant une exploration de la function thyroïdienne. [Torres, S.M.F. Hypothyroidism in a dog associated with triméthoprim-sulphadiazine therapy (Hypothyroi'die en relation avec un traitement triméthoprim-sulphadiazine chez un chien). Veterinary Dermatology 1996; 7 : 105–108.] Resumen Un perro Golden Retriever de 4 años desarrolló hipotiroidismo y una afección neuromuscular después de recibir un tratamiento con sulfonamidas potenciadas y metronidazol 18 y 14 semanas, respectivamente. Las concentraciones séricas totales de T4 eran indetectables antes y a las 6 horas después de la administración exógena de 4 UI de TSH bovina. La biopsia de tiroides mostró alteraciones indicativas de gota hiperplásica difusa. Las concentraciones séricas de T4 fueron normales a los 7 dias de retirar la terapia. La terapia prolongada con trimetoprim-sulfadiazina fue considerada la causa más probable de gota hiperplásica en este perro. No se determinó la causa del cuadro neuromuscular. Se recomienda retirar la terapia con sulfonamida potenciada al menos 7 días antes de la evaluación de la función tiroidea. [Torres, S.M.F. Hypothyroidism in a dog associated with trimethoprim-sulphadiazine therapy (Hipotiroidismo en un perro asociado a la terapia con trimetoprim-sulfadiazina). Veterinary Dermatology 1996; 7 : 105–108.] Zusammenfassung— Hypothyreose und eine neuromuskuläre Störung entwickelten sich bei einem 4 Jahre alten Golden Retriever, nachdem er potenzierte Sulfonamide und Metronidazol über 18 beziehungsweise 14 Wochen erhalten hatte. Die Gesamt T4-Konzentrationen waren vor und 6 Stunden nach exogener Verabreichung von 4 IE bovinen TSH nicht meßbar. Eine Biopsie der Schilddrüse zeigte Veränderungen, die parallel mit diffusem hyperplasischem Kropf auftreten. Die Serum T4-Konzentrationen waren 7 Tage nach Abbruch der Therapie wieder normal. Die Langzeit-Trimethoprim-Sulfadiazin-Therapie wurde als wahr-scheinlichste Ursache dieses hyperplastischen Kropfes beim Hund angesehen. Die Ursache der neuro-muskulären Störung konnte nicht festgestellt werden. Es wird empfohlen, potenzierte Sulfonamide mindestens 7 Tage vor einer überprüfung der Schilddrüsenfunktion abzusetzen. [Torres, S. M. F. Hypothyroidism in a dog associated with trimethoprim-sulphadiazine therapy (Hyperthyreose bei einem Hund in Verbindung mit einer Trimethoprim-Sulfadiazin-Therapie). Veterinary Dermatology 1996; 7 : 105–108.]     

A novel mutation of the CLCN1 gene associated with myotonia hereditaria in an Australian cattle dog

BACKGROUND: Heritable myotonia is a genetic muscle disorder characterized by slow relaxation of skeletal muscles. The main clinical signs are skeletal muscle stiffness, especially after vigorous contraction, and muscle hypertrophy. Muscle stiffness may be enhanced by inactivity, and often is relieved by exercise. Myotonia can be inherited in an autosomal dominant or recessive manner (Thomsen- or Becker-type myotonia, respectively). In mice, goats, Miniature Schnauzer dogs, and most affected humans, the disorder is caused by mutations in CLCN1, which encodes the skeletal muscle voltage-gated chloride channel, Cl1C-1. HYPOTHESIS: We hypothesized that an Australian Cattle Dog with generalized muscle stiffness and hypertrophy examined at the Ontario Veterinary College would have a mutation in the CLCN1 gene. ANIMALS: A pure-bred Australian Cattle Dog from Ontario, Canada, was used. METHODS: Based on clinical signs and electromyographic test results, a diagnosis of myotonia hereditaria was made, and a muscle biopsy was collected for genetic analysis. RESULTS: Sequence data obtained from the affected dog confirmed that it was homozygous for a single base insertion in the CLCN1 coding sequence. This mutation would result in a truncated ClC-1 protein being expressed, which, based on molecular evidence from other studies, would result in functionally compromised chloride conduction in the skeletal muscles of the animal. CONCLUSIONS AND CLINICAL IMPORTANCE: To the authors' knowledge, this report describes the Ist case of myotonia in an Australian Cattle Dog and represents the 1st non-Schnauzer canine myotonia to be genetically characterized. In addition, we developed a polymerase chain reaction-based genetic screen to detect heterozygotes with this mutation in the at-large Australian Cattle Dog population.     

Evaluation of canine heat shock transcription factor 4 (HSF4) as a candidate gene for primary cataracts in the Dachshund and the Entlebucher Mountain dog

OBJECTIVE: Testing of the cataract-causing insertion/deletion mutation in the canine HSF4 gene for its linkage and association with primary cataracts (CAT) in Dachshunds and Entlebucher Mountain dogs. MATERIALS: Exon 9 with flanking intronic regions of the canine HSF4 gene was sequenced in 24 Dachshunds and 20 Entlebucher Mountain dogs. The HSF4 cDNA sequence of lens tissue was analyzed in a CAT-unaffected mixed-breed dog and in three CAT-affected dogs of different breeds, including a Wire-haired Dachshund, a Dachshund-mix and a German Shepherd dog. RESULTS: In all dogs investigated here, the previously reported CAT-causing mutation did not exist. We found a single nucleotide polymorphism (SNP) in intron 9, which was neither associated nor linked with the CAT phenotype in the two dog breeds. CONCLUSION: The CAT phenotype in the two dog breeds investigated here was not caused by the same mutation found to be associated with early-onset CAT in the Staffordshire Bull Terrier and Boston Terrier. The intronic SNP may be useful to test HSF4 for linkage with CAT in further dog breeds.     

Effects of a P2Y(12) receptor antagonist on the response of equine platelets to ADP. Comparison with human platelets

Horses show susceptibility to platelet-related disorders. Equine platelets differ from human platelets in some of their responses, so information available about human platelets must be validated in the horse. Aggregation of platelets by ADP involves both P2Y(1) and P2Y(12) receptors on the platelet surface. We have compared the effect of the P2Y(12) antagonist, AR-C67085, on equine and human platelets in vitro using turbidimetric aggregometry to measure the rate and final extent of aggregation. Aggregation profiles, concentration-response curves and pA(2) values show that the rate of aggregation of equine platelets is much more susceptible to inhibition by AR-C67085 than that of human platelets. This species difference may reflect differences in the relative numbers of P2Y(1) and P2Y(12) receptors, or in intracellular signalling pathways, but will need to be considered by equine clinicians before using P2Y(12) antagonists in the treatment of thrombotic conditions.     

Association of a missense mutation in the luteinizing hormone/choriogonadotropin receptor gene （LHCGR） with superovulation traits in Chinese Holstein heifers

Background: Upon binding luteinizing hormone in the ovary, the luteinizing hormone/choriogonadotropin receptor (LHCGR) is necessary for follicular maturation and ovulation, as well as luteal function. We detected mutations in the LHCGR gene and evaluated their association with superovulation. Methods: Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, we examined polymorphisms in LHCGR and the genotypes associated with superovulation traits in 127 Chinese Holstein heifers. Results: A G/T polymorphism (ss52050737) in exon 11 was significantly associated with the total number of ova and the number of transferable embryos. Conclusions: LHCGR may be a new predictor for superovulation in Chinese Holstein heifers.     

An insertion/deletion variant of a thymine base in exon 2 of the porcine beta 3‐adrenergic receptor gene associated with loin eye muscle area

An insertion/deletion variant of a thymine base (T5 and T6) in exon 2 of porcine beta 3‐adrenergic receptor (ADRB3) gene has been described. In the current study, we made an association study between the ADRB3 polymorphisms and production traits in 735 Duroc pigs. The allele frequencies for the T5 and T6 alleles in our study population were 0.433 and 0.567, respectively. Any associations between ADRB3 genotype and average daily weight gain during test period, or backfat thickness and intramuscular fat content were not detected in either sex. However the size of the loin eye muscle area (EMA) was significantly associated with ADRB3 genotypes in gilts. T6‐homozygous gilts had a higher mean of EMA (40.6 ± 0.6 cm²) than T5‐homozygous (38.1 ± 0.4 cm², P = 0.002) and heterozygous (38.8 ± 0.3 cm², P = 0.034) gilts. This association was not detected in males. In addition, a multiple traits animal model best linear unbiased predictor (BLUP) analysis revealed that the T6‐homozygous genotype had positive effects on breeding value of EMA. Accordingly, we suggest that ADRB3 polymorphism has the potential to be an important genetic marker for prediction of EMA in Duroc pigs.     

A novel 86-bp indel of the motilin receptor gene is significantly associated with growth and carcass traits in Gushi-Anka F2 reciprocal cross chickens

ABSTRACT

1. A previous whole-genome association analysis has identified the motilin receptor gene (MLNR), which regulates gastrointestinal motility and gastric emptying, as a candidate gene related to chicken growth.

2. MLNR mRNA was expressed in all tissues tested, and the expression level in digestive tissues was greater than in other tissues. Expression levels in the pancreas, duodenum and glandular stomach at day old and one, two and three weeks of age indicated a possible correlation with the digestive system. This suggested that the MLNR gene plays a central role in gastrointestinal tract function and affects the growth and development of chickens. Moreover, there was a significant difference in expression in the glandular stomach tissue between Ross 308 and Gushi chickens at six weeks of age.

3. Re-sequencing revealed an 86-bp insertion/deletion polymorphism in the downstream region of the MLNR gene. The mutation locus was genotyped in 2,261 individuals from nine different chicken breeds. MLNR expression levels in the glandular stomach of chickens with DD genotypes were greater than those in chickens with the ID and II genotypes. The DD genotype was the most dominant genotype in commercial broiler's (Ross 308 and Arbor Acres broilers), and the D allele frequency in these breeds exceeded 91%. The deletion mutation tended towards fixation in commercial broilers.

4. Association with growth and carcass traits analysed in a Gushi-Anka F₂ intercrossed population, showed that the DD genotype was significantly associated with the greatest growth and carcass trait values, whereas values associated with the II genotype were the lowest in the F₂ reciprocal cross chickens.

5. The results suggest that the mutation is strongly associated with growth related traits and it is likely to be useful for marker-assisted selection of chickens.