Taurine deficiency in maned wolves (Chrysocyon brachyurus) maintained on two diets manufactured for prevention of cystine urolithiasis

This study assesses the long‐term effects of an experimental diet vs. a commercially available manufactured diet, intended to reduce clinical disease related to cystinuria, on the taurine status of captive maned wolves. For 13 weeks, two pairs of maned wolves were maintained on the commercially available maintenance diet, whereas two individually housed wolves were maintained on the experimental diet. All six wolves, at the beginning and at the end of the diet trial, had severely decreased plasma concentrations of taurine (as compared to the normal canine reference range of 60–120 nmol/ml) (National Research Council [2003] National Academies Press) with average taurine concentrations of 16 nmol/ml at the beginning of the study and 3 nmol/ml at the end of the study. There was no statistically significant difference in the taurine concentrations between animals on the maintenance vs. experimental diets. Both diets were supplemented subsequently with taurine at a concentration of 0.3%. All study animals were eventually switched to the taurine‐supplemented version of the commercially manufactured maintenance diet and subsequent samplings were carried out to monitor plasma taurine concentrations. A final sampling, carried out approximately 5 months after the initiation of taurine supplementation, showed an average taurine concentration within the target canine reference range (90.25 nmol/ml). There are numerous physiologic (e.g., possible unique metabolism and requirements for taurine in this species as compared to other canids) and dietary factors (e.g., effects of the types and concentrations of fiber and protein on nutrient availability, taurine metabolism, and enterohepatic circulation of taurine‐conjugated bile salts; impaired taurine synthesis secondary to low cysteine availability) that could be potential contributors to the development of taurine deficiency in the maned wolves in this study. Taurine supplementation should be considered in maned wolves maintained on diets intended for reduction of cystinuria‐related complications. Zoo Biol 0:1–14, 2005. © 2005 Wiley‐Liss, Inc.     

Focus: Rare Disease: Cystinuria: Review of a Life-long and Frustrating Disease

Cystinuria, accounting for about 1-2% of kidney stones in adults, carries significant morbidity beginning at a young age [1]. Cystine stone formers have more stone events compared to other stone formers, as well as more surgical interventions, potentially contributing to faster progression to chronic kidney disease (CKD), and end-stage kidney disease (ESKD) [2]. Successful medical therapy for cystine stone formers may be limited by adherence to the extensive lifestyle changes and the adverse side effect profiles of some interventions, leading to decreased quality of life for these patients relative to other stone formers.     

Amino acid transport systems of lysosomes: Possible substitute utility of a surviving transport system for one congenitally defective or absent

Ways in which other transport systems may compensate for one that is genetically defective are considered. Comparisons of the transport systems of organelles (here the lysosome) with the transport system at the plasma membrane has significant implications for chemotherapy.     

CRISPR/Cas9 engineering of albino cystinuria Type A mice

Cystinuria Type A is a relatively common genetic kidney disease occurring in 1 in 7,000 people worldwide that results from mutation of the cystine transporter rBAT encoded by Slc3a1. We used CRISPR/Cas9 technology to engineer cystinuria Type A mice via genome editing of the C57BL/6NHsd background. These mice are an improvement on currently available models as they are on a coisogenic genetic background and have a single defined mutation. In order to use albinism to track Cas9 activity, we co‐injected gRNAs targeting Slc3a1 and tyrosinase (Tyr) with Cas9 expressing plasmid DNA into mouse embryos. Two different Slc3a1 mutational alleles were derived, with homozygous mice of both demonstrating elevated urinary cystine levels, cystine crystals, and bladder stones. We used whole genome sequencing to evaluate for potential off‐target editing. No off‐target indels were observed for the top 10 predicted off‐targets for Slc3a1 or Tyr. Therefore, we used CRISPR/Cas9 to generate coisogenic albino cystinuria Type A mice that could be used for in vivo imaging, further study, or developing new treatments of cystinuria.     

Feed intake and digestion in the maned wolf (Chrysocyon brachyurus): Consequences for dietary management

Captive maned wolves (Chrysocyon brachyurus) often consume diets high in prey and meat items even though they are omnivorous in the wild. These soft, high protein diets may exacerbate conditions of gingivitis and cystinuria in this species. Feed intakes were monitored in wolves provided with prey and meat-based diets (3 periods) and subsequently with extruded dog chows and small amounts of prey (2 periods). Digestibilities of each type of diet were measured with the indigestible marker chromic oxide. Dry matter intakes were similar between diets (374–584 g · 30 kg^?1 · d^?1), even though dietary protein content was reduced from 44% to 29% of dry matter. Digestibility of dry matter was unaltered by these dietary changes (77% of high prey diet vs. 73% of chow diet), but fecal consistency changed to softer stools at lower intakes of prey. Estimated metabolizable energy intakes of wolves (501–674 kJ · kg^?0.75 · d^?1) were similar to the maintenance requirement for domestic dogs (525 kJ · kg^?0.75 · d^?1), suggesting a similar energy requirement for maintenance of the wolves. The metabolizable energy derived from protein in the high prey diets was 37%, whereas that of the chow diets was only 27%. These levels exceed estimates of protein requirements for maintenance (4.3–21.8%) and growth (11.5–20.3%) in domestic dogs and may thus exceed those of the wolves. Dietary management of maned wolves should minimize excess protein intake by limiting prey consumption and acclimating animals to extruded diets for domestic dogs. Further research is required to formulate diets for long-term management of cystinuria in maned wolves. © 1994 Wiley-Liss, Inc.