Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia)

A canine model of glycogen storage disease Ia (GSD Ia), similar clinically, biochemically, and pathologically to the human disease, was established by crossbreeding Maltese and Beagle dogs carrying a mutated, defective glucose-6-phosphatase (G-6-Pase) gene. Ten puppies were born in three litters from these crossbreedings. Six were homozygous for the previously described M121I GSD Ia mutation. Of these six affecteds, two were stillborn, and one died at 2, 32, and 60 days of life, respectively (puppies A, B, C, D, E), while one is alive at age 15 months (puppy F). Affected puppies exhibited tremors, weakness, and neurologic signs when hypoglycemic. They had postnatal growth retardation and progressive hepatomegaly. Biochemical abnormalities included fasting hypoglycemia, hyperlactacidemia, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Microscopic examination of tissues from affected puppies showed diffuse, marked hepatocellular vacuolation, with distended clear hepatocytes and central to marginally located rounded nuclei. In the kidneys of puppies D and E, there was segmental glomerular sclerosis and vacuolation of proximal convoluted tubular epithelium. Biochemical analysis revealed increased liver glycogen content and isolated markedly reduced G-6-Pase enzyme activity in liver and kidney. The canine G-6-Pase gene was characterized by screening a canine genomic library. It spans approximately 11.8 kb and consists of five exons with >90% amino acid sequence homology to the derived human sequence. The first 1.5 kb of the 5' region was sequenced and contains several putative response element motifs homologous to the human 5' region. Establishment of this canine colony of GSD Ia that closely resembles human disease and isolation of the canine genomic gene provides an excellent model for studying pathophysiology and long-term complications and an opportunity to develop novel therapeutic approaches such as drug and gene therapy.     

Genetic analysis of eutypa strains from california supports the presence of two pathogenic species

ABSTRACT Eutypa dieback is a perennial canker disease that adversely affects grape (Vitis vinifera) production throughout the world. The causal agent has been known as either Eutypa armeniacae or E. lata, and it has been unclear whether the two taxa are separate species. We analyzed 115 isolates of Eutypa and conspecific strains, including 106 from California, using amplified fragment length polymorphism (AFLP) and sequence analysis of the ribosomal DNA (rDNA) internal transcribed spacer (ITS) sequence. Strains from cultivated plant species exhibited an average genetic distance of 0.34, as calculated by the DICE coefficient (NTSYS-pc software). An unweighted pair-group method with arithmetic averages dendrogram revealed a genetically distinct (distance of 0.73) group of Eutypa strains from valley oak (Quercus lobata) and madrone (Arbutus menziesii) and a strain from grape. Analysis of rDNA ITS sequences strongly supported the genetically distinct cluster detected in the AFLP data. Combined data indicated the presence of two species of Eutypa (E. armeniacae and E. lata) in our sample population. However, both Eutypa species were capable of infecting native and cultivated hosts, suggesting the potential for native tree species to serve as inoculum sources for grape infection in California. Further investigations of E. armeniacae and E. lata would contribute to the development of a successful disease management strategy.     

Nonneurogenic urinary incontinence in a canine female pseudohermaphrodite

Nonneurogenic incontinence was observed in a 1-year-old Pekingese X Poodle with female pseudohermaphroditism. The dog had male external genitalia as well as a well-developed vagina, uterus, and ovaries. Urinary incontinence was caused by an anomalous communication of the prostatic urethra with the vagina. Ovariohysterectomy and surgical correction of the urethrovaginal fistula was followed by remission of urinary incontinence. Subsequently, the dog developed estrogen responsive urinary incontinence. Nonneurogenic incontinence to be a common finding in canine pseudohermaphroditism associated with abnormalities of the vagina or urethra (or both). Surgical correction should be considered to correct anomalous communications between the genital and lower urinary tracts.