The biogenic amine octopamine is synthesized from both tyrosine and tyramine in the lateral, median, and ventral eyes of Limulus. The autoradiographic studies presented here were designed to locate the sites of octopamine synthesis in the ventral and lateral eyes. We found that efferent fibers, which project to ventral and lateral eyes from the central nervous system, became intensely and selectively labeled during in vitro incubations with 3H-tyramine. In the ventral eye, more than 95% of the efferent fibers were labeled. Results of biochemical analyses suggested that most of the radioactive substance within these efferent fibers was newly synthesized octopamine. The selective labeling of efferent fibers during incubation with 3H-tyramine was used as an anatomical tool to study the number and distribution of efferent fibers within the ventral eye. Light microscopic (LM) reconstructions of the distribution of label in serial longitudinal sections through ventral optic nerves together with electron microscopic (EM) autoradiographic analyses revealed between 70 and 200 efferent axons. The results of these studies and of reconstructions of efferent innervation to photoreceptor somata suggest that each ventral photoreceptor cell or each small cluster of cells is innervated by a separate efferent fiber. Both LM reconstructions and EM analyses showed that efferent fibers ramify extensively and specifically in and near the internal rhabdom of ventral photoreceptor cells. In EM autoradiographs of lateral eyes incubated with 3H- tyramine, the silver grains that were located over ommatidia were concentrated exclusively over efferent fibers. All of these efferent fibers, which lay near rhabdoms and in partitions between retinular cells, were labeled. The results of our present studies support our hypothesis that octopamine is a neurotransmitter in Limulus retinal efferent fibers. This amine may modulate the biochemistry and physiology of ventral photoreceptor cells and may mediate many of the known effects of circadian efferent innervation to the lateral eye.
BackgroundThe antisense insertion of a canine short interspersed element (SINEC_Cf) in the pigmentation gene PMEL (or SILV) causes a coat pattern phenotype in dogs termed merle. Merle is a semi-dominant trait characterized by patches of full pigmentation on a diluted background. The oligo(dT) tract of the Merle retrotransposon is long and uninterrupted and is prone to dramatic truncation. Phenotypically wild-type individuals carrying shorter oligo(dT) lengths of the Merle allele have been previously described and termed cryptic merles. Two additional coat patterns, dilute merle (uniform, steely-grey coat) and harlequin merle (white background with black patches), also appear in breeds segregating the Merle allele.ResultsSequencing of all PMEL exons in a dilute and a harlequin merle reveals that variation exists solely within the oligo(dT) tract of the SINEC_Cf insertion. In fragment analyses from 259 dogs heterozygous for Merle, we observed a spectrum of oligo(dT) lengths spanning 25 to 105 base pairs (bp), with ranges that correspond to the four varieties of the merle phenotype: cryptic (25–55 bp), dilute (66–74 bp), standard (78–86 bp), and harlequin (81–105 bp). Somatic contractions of the oligo(dT) were observed in 43% of standard and 51% of harlequin merle dogs. A small proportion (4.6%) of the study cohort inherited de novo contractions or expansions of the Merle allele that resulted in dilute or harlequin coat patterns, respectively.ConclusionsThe phenotypic consequence of the Merle SINE insertion directly depends upon oligo(dT) length. In transcription, we propose that the use of an alternative splice site increases with oligo(dT) length, resulting in insufficient PMEL and a pigment dilution spectrum, from dark grey to complete hypopigmentation. We further propose that during replication, contractions and expansions increase in frequency with oligo(dT) length, causing coat variegation (somatic events in melanocytes) and the spontaneous appearance of varieties of the merle phenotype (germline events).Electronic supplementary materialThe online version of this article (10.1186/s13100-018-0131-6) contains supplementary material, which is available to authorized users.
Dogs are second only to humans in medical surveillance and preventative health care, leading to a recent perception of increased cancer incidence. Scientific priorities in veterinary oncology have thus shifted, with a demand for cancer genetic screens, better diagnostics, and more effective therapies. Most dog breeds came into existence within the last 300 years, and many are derived from small numbers of founders. Each has undergone strong artificial selection, in which dog fanciers selected for many traits, including body size, fur type, color, skull shape, and behavior, to create novel breeds. The adoption of the breed barrier rule—no dog may become a registered member of a breed unless both its dam and its sire are registered members—ensures a relatively closed genetic pool within each breed. As a result, there is strong phenotypic homogeneity within breeds but extraordinary phenotypic variation between breeds. One consequence of this is the high level of breed-associated genetic disease. We and others have taken advantage of this to identify genes for a large number of canine maladies for which mouse models do not exist, particularly with regard to cancer.
The role of the nurse manager is pivotal in creating a work environment in which nurse-physician collaboration is the expected norm. It is the nurse manager who clarifies the vision of collaboration, practices as a role model for collaboration, and inspires others to achieve this difficult goal. In addition, the nurse manager manipulates the environmental resources and facilitates self-confidence of staff. The management paradigm that unites the work environment with individual ability is most likely to facilitate collaborative practice.
The lack of an annotated reference sequence for the canine Y chromosome has limited evolutionary studies, as well as our understanding of the role of Y-linked sequences in phenotypes with a sex bias. In genome-wide association studies (GWASs), we observed spurious associations with autosomal SNPs when sex was unbalanced in case-control cohorts and hypothesized that a subset of SNPs mapped to autosomes are in fact sex-linked. Using the Illumina 230K CanineHD array in a GWAS for sex, we identified SNPs that amplify in both sexes but possess significant allele frequency differences between males and females. We found 48 SNPs mapping to 14 regions of eight autosomes and the X chromosome that are Y-linked, appearing heterozygous in males and monomorphic in females. Within these 14 regions are eight genes: three autosomal and five X-linked. We investigated the autosomal genes (MITF, PPP2CB, and WNK1) and determined that the SNPs are diverged nucleotides in retrocopies that have transposed to the Y chromosome. MITFY and WNK1Y are expressed and appeared recently in the Canidae lineage, whereas PPP2CBY represents a much older insertion with no evidence of expression in the dog. This work reveals novel canid Y chromosome sequences and provides evidence for gene transposition to the Y from autosomes and the X.
Background: Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission that may be presynaptic, synaptic, or postsynaptic. Causative mutations have been identified in 4 breeds including the Labrador Retriever, Jack Russell Terrier, Heideterrier, and Danish Pointing Dog.Hypothesis/Objective: Clinical and genetic characterization of a neuromuscular disorder in Golden Retriever (GR) puppies.Animals: Four GR puppies from California were evaluated for generalized muscle weakness beginning at weaning. Biological specimens were collected from the affected puppies, and familial information was obtained. Blood or buccal swabs were obtained from 63 unaffected GRs.Methods: Complete physical, neurological, electrodiagnostic, and histological evaluations and biochemical quantification of muscle acetylcholine receptors were performed. Polymerase chain reaction was used to amplify the 17 exons of COLQ, and sequences were obtained by Sanger sequencing. Variant frequency was assessed in unrelated GRs and a public database.
Background: Limb-girdle muscular dystrophies (LGMDs) are a heterogeneous group of inherited autosomal myopathies that preferentially affect voluntary muscles of the shoulders and hips. LGMD has been clinically described in several breeds of dogs, but the responsible mutations are unknown. The clinical presentation in dogs is characterized by marked muscle weakness and atrophy in the shoulder and hips during puppyhood. Methods: Following clinical evaluation, the identification of the dystrophic histological phenotype on muscle histology, and demonstration of the absence of sarcoglycan-sarcospan complex by immunostaining, whole exome sequencing was performed on five Boston terriers: one affected dog and its three family members and one unrelated affected dog. Results: Within sarcoglycan-δ (SGCD), a two base pair deletion segregating with LGMD in the family was discovered, and a deletion encompassing exons 7 and 8 was found in the unrelated dog. Both mutations are predicted to cause an absence of SGCD protein, confirmed by immunohistochemistry. The mutations are private to each family. Conclusions: Here, we describe the first cases of canine LGMD characterized at the molecular level with the classification of LGMD2F.
Nemaline myopathy (NM) is a congenital muscle disorder associated with muscle weakness, hypotonia, and rod bodies in the skeletal muscle fibers. Mutations in 10 genes have been implicated in human NM, but spontaneous cases in dogs have not been genetically characterized. We identified a novel recessive myopathy in a family of line-bred American bulldogs (ABDs); rod bodies in muscle biopsies established this as NM. Using SNP profiles from the nuclear family, we evaluated inheritance patterns at candidate loci and prioritized TNNT1 and NEB for further investigation. Whole exome sequencing of the dam, two affected littermates, and an unaffected littermate revealed a nonsense mutation in NEB (g.52734272 C>A, S8042X). Whole tissue gel electrophoresis and western blots confirmed a lack of full-length NEB in affected tissues, suggesting nonsense-mediated decay. The pathogenic variant was absent from 120 dogs of 24 other breeds and 100 unrelated ABDs, suggesting that it occurred recently and may be private to the family. This study presents the first molecularly characterized large animal model of NM, which could provide new opportunities for therapeutic approaches.
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