Mucopolysaccharidosis type VII in a German Shepherd Dog

A 12-week-old male German Shepherd Dog was evaluated because of a 3-week history of a progressive inability to ambulate. Clinical and laboratory findings included skeletal deformities, corneal cloudiness, cytoplasmic granules in the neutrophils and lymphocytes of blood and CSF and glycosaminoglycans in a urine sample (detected via a toluidine blue spot test). Enzyme activity and DNA analyses confirmed mucopolysaccharidosis type VII as a result of severe beta-glucuronidase deficiency; this condition had been identified in a mixed-breed dog (likely of German Shepherd Dog descent) that was reported 20 years earlier and caused by the same missense mutation. Because of the progressive nature of this disease, the puppy was euthanatized and all tissues examined contained evidence of lysosomal storage leading to marked cellular distention. Mucopolysaccharidosis type VII is only one of many hereditary lysosomal storage diseases identified in companion animals. It is important that clinicians recognize the typical signs of lysosomal storage diseases and are aware of the cytologic and urinary screening tests for mucopolysaccharidosis disorders. Furthermore, there are specific blood enzyme and DNA-based tests to distinguish the forms of mucopolysaccharidosis in affected and carrier animals.     

Isolation and characterization of pediatric canine bone marrow CD34+ cells

Historically, the dog has been a valuable model for bone marrow transplantation studies, with many of the advances achieved in the dog being directly transferable to human clinical bone marrow transplantation protocols. In addition, dogs are also a source of many well-characterized homologues of human genetic diseases, making them an ideal large animal model in which to evaluate gene therapy protocols. It is generally accepted that progenitor cells for many human hematopoietic cell lineages reside in the CD34+ fraction of cells from bone marrow, cord blood, or peripheral blood. In addition, CD34+ cells are the current targets for human gene therapy of diseases involving the hematopoietic system. In this study, we have isolated and characterized highly enriched populations of canine CD34+ cells isolated from dogs 1 week to 3 months of age. Bone marrow isolated from 2- to 3-week-old dogs contained up to 18% CD34+ cells and this high percentage dropped sharply with age. In in vitro 6-day liquid suspension cultures, CD34+ cells harvested from 3-week-old dogs expanded almost two times more than those from 3-month-old dogs and the cells from younger dogs were also more responsive to human Flt-3 ligand (Flt3L). In culture, the percent and number of CD34+ cells from both ages of dogs dropped sharply between 2 and 4 days, although the number of CD34+ cells at day 6 of culture was higher for cells harvested from the younger dogs. CD34+ cells harvested from both ages of dogs had similar enrichment and depletion values in CFU-GM methylcellulose assays. Canine CD34+/Rho123lo cells expressed c-kit mRNA while the CD34+/Rhohi cells did not. When transplanted to a sub-lethally irradiated recipient, CD34+ cells from 1- to 3-week-old dogs gave rise to both myeloid and lymphoid lineages in the periphery. This study demonstrates that canine CD34+ bone marrow cells have similar in vitro and in vivo characteristics as human CD34+ cells. In addition, ontogeny-related functional differences reported for human CD34+ cells appear to exist in the dog as well, suggesting pediatric CD34+ cells may be better targets for gene transfer than adult bone marrow. The demonstration of similarities between canine and human CD34+ cells enhances the dog as a large, preclinical model to evaluate strategies for improving bone marrow transplantation protocols, for gene therapy protocols that target CD34+ cells, and to study the engraftment potential of various cell populations that may contain hematopoietic progenitor cell activity.     

The caprine oxyhemoglobin dissociation curve

The caprine oxyhemoglobin dissociation curve has not been previously defined. Blood from 10 healthy goats was equilibrated in a tonometer with calibrated gas mixtures of oxygen at concentrations of 95%, 21%, 13%, 12%, 10%, 9%, 8%, 5%, 4%, and 2.5% , 5% carbon dioxide, balance nitrogen. The pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), total hemoglobin, oxyhemoglobin saturation, carboxyhemoglobin, methemoglobin, and oxygen content were measured. The PO2/oxyhemoglobin and the PO2/oxygen content relationships were graphed with curve-fitting software and a formula for calculating oxyhemoglobin from PO2 was generated. The maximum oxygen content per gram of hemoglobin was 1.29 ml of oxygen per gram of hemoglobin. The PO2 at which hemoglobin was 50% saturated (P50) from the PO2/oxyhemoglobin relationship was 28.6+/-1.5 mmHg and that from the PO2/oxygen content relationships was 29.1+/-1.6 mmHg. The Hill coefficient for the PO2/oxyhemoglobin data was 3.0+/-0.4.     

Letters to the editor

Extract

In order to utilize spring growth efficiently under a system of grassland farming, a New Zealand dairy farmer endeavours to calve as many cows as possible within a four to six weeks' period. To maintain this calving pattern, herd members must conceive by 70 to 80 days after calving. Consequently normal postparturient uterine involution, together with a minimum of delay in the onset of ovarian activity and oestral cyclicity, is of vital importance. A study of these phenomena may be very rewarding in helping to achieve optimal reproductive efficiency.     

Letters to the editor

Extract

Sir,—A 7-month-old lamb was presented for slaughter, one of a line of 460. The animal was in good condition and, except for a moderately enlarged abdomen, no abnormalities could be detected on ante-mortem examination.