Cloning, function, and localization of human, canine, and Drosophila ZIP10 (SLC39A10), a Zn2+ transporter

Zinc (Zn2+) is the second most abundant trace element, but is considered a micronutrient, as it is a cofactor for many enzymes and transcription factors. Whereas Zn2+ deficiency can cause cognitive immune or metabolic dysfunction and infertility, excess Zn2+ is nephrotoxic. As for other ions and solutes, Zn2+ is moved into and out of cells by specific membrane transporters: ZnT, Zip, and NRAMP/DMT proteins. ZIP10 is reported to be localized at the apical membrane of renal proximal tubules in rats, where it is believed to play a role in Zn2+ import. Renal regulation of Zn2+ is of particular interest in light of growing evidence that Zn2+ may play a role in kidney stone formation. The objective of this study was to show that ZIP10 homologs transport Zn2+, as well as ZIP10, kidney localization across species. We cloned ZIP10 from dog, human, and Drosophila (CG10006), tested clones for Zn2+ uptake in Xenopus oocytes and localized the protein in renal structures. CG10006, rather than foi (fear-of-intimacy, CG6817) is the primary ZIP10 homolog found in Drosophila Malpighian tubules. The ZIP10 antibody recognizes recombinant dog, human, and Drosophila ZIP10 proteins. Immunohistochemistry reveals that ZIP10 in higher mammals is found not only in the proximal tubule, but also in the collecting duct system. These ZIP10 proteins show Zn2+ transport. Together, these studies reveal ZIP10 kidney localization, a role in renal Zn2+ transport, and indicates that CG10006 is a Drosophila homolog of ZIP10

Urinary metals in a spontaneous canine model of calcium oxalate urolithiasis.

Calcium oxalate urolithiasis is a common and painful condition in people. The pathogenesis of this disease is complex and poorly understood. Laboratory animal and in vitro studies have demonstrated an effect of multiple trace metals in the crystallization process, and studies in humans have reported relationships between urinary metal concentrations and stone risk. Dogs are a spontaneous model of calcium oxalate urolithiasis, and the metal content of canine calcium oxalate stones mirrors that of human stones. The aim of this study was to test for a relationship between urinary metals and calcium oxalate urolithiasis in dogs. We hypothesized that urinary metals would differ between dogs with and without calcium oxalate urolithiasis. Urine from 122 dogs (71 cases and 51 stone-free controls) was analyzed for calcium and 12 other metals. The cases had higher urinary calcium, copper, iron, and vanadium and lower urinary cobalt. Higher urinary vanadium in the cases was associated with being fed a therapeutic stone-prevention diet. Urinary calcium had a strong positive correlation with strontium and moderate positive correlations with chromium, nickel, and zinc. The results of this study complement the findings of similar human studies and suggest a potential role of trace metals in calcium oxalate urolithiasis. Further investigation into how trace metals may affect stone formation is warranted

Spontaneous remission and relapse of diabetes mellitus in a male dog

Abstract An 8‐year‐old male neutered Miniature Schnauzer was diagnosed with diabetes mellitus based on fasting hyperglycemia and glucosuria after a 2‐week history of polydipsia and periuria, in line with the Agreeing Language in Veterinary Endocrinology consensus definition. Treatment of insulin and dietary management was initiated. The insulin dose was gradually reduced and eventually discontinued over the next year based on spot blood glucose concentrations that revealed euglycemia or hypoglycemia. After discontinuation, the dog remained free of clinical signs for 1 year until it was again presented for polyuria/polydipsia with fasting hyperglycemia and glucosuria. Insulin therapy was resumed and continued for the remainder of the dog's life. Although diabetic remission often occurs in cats and humans, the presumed etiopathogenesis of pancreatic beta cell loss makes remission rare in dogs, except for cases occurring with diestrus or pregnancy. This case demonstrates that diabetic remission is possible in dogs, even in cases without an identifiable reversible trigger

Prevalence and Predictors of Radiographically Apparent Upper Urinary Tract Urolithiasis in Eight Dog Breeds Predisposed to Calcium Oxalate Urolithiasis and Mixed Breed Dogs

Data on upper urinary tract (UUT) uroliths in dogs are important to understanding their etiology. The aim of this retrospective case-control study was to determine the prevalence and identify predictors of radiographically apparent UUT uroliths in dog breeds at increased risk for calcium oxalate uroliths (CaOx risk breeds) and mixed breed dogs. Radiologist reports of three-view abdominal radiographs were reviewed from 251 purebred dogs of 8 CaOx risk breeds and 68 mixed breed dogs. UUT uroliths were more common in CaOx risk breeds than mixed breed dogs (23% versus 6%, respectively; OR = 4.8, 95% confidence interval [CI] 1.7–18.9, p < 0.001). UUT uroliths were more common in dogs with lower urinary tract (LUT) uroliths (predominantly calcium-containing) than those without (41% versus 5%, respectively; OR = 13.6, 95% CI 6.3–33.1, p < 0.001), and LUT uroliths predicted the presence of UUT uroliths in the multivariable regression (OR = 6.5, 95% CI 2.8–16.7, p < 0.001). Increasing age (p < 0.001) and lower body weight (p = 0.0016) were also predictors of UUT urolith presence in the multivariable regression. The high prevalence of UUT uroliths in dogs with LUT uroliths supports a shared mechanism for their formation

Heat map of correlation coefficients between urinary metals in dogs with and without CaOx urolithiasis.

<p>Correlation coefficients in bold font had p-values < 0.05.</p

Reduced multivariable regression models for the effects of CaOx stone status and environmental factors on log-transformed urinary element-to-creatinine ratios (Ca/Cre, Co/Cre, Cu/Cre, Fe/Cre and V/Cre).

<p>For variables with 1 degree of freedom, the status corresponding to the estimate is in parentheses.</p

Urinary element-to-creatinine ratios in dogs with CaOx urolithiasis (cases) and stone-free controls.

<p>Values are reported in mg/g for urinary Ca/Cre and μg/g for the other urinary element-to-creatinine ratios.</p

Characteristics of the 122 study dogs.

<p>Cases are dogs with confirmed CaOx urolithiasis, and controls are stone-free as determined by abdominal radiography. Age at the time of urine sampling is reported as mean ± standard deviation, and weight is reported as median (range).</p

Box and whisker plots of urinary A) calcium-to-creatinine (Ca/Cre, mg/g), B) cobalt-to-creatinine (Co/Cre, μg/g), C) copper-to-creatinine (Cu/Cre, μg/g), and D) iron-to-creatinine (Fe/Cre, μg/g), and E) vanadium-to-creatinine (V/Cre, μg/g) ratios for dogs with a history of CaOx stones (cases) and stone-free dogs (controls).

<p>The boxes represent the interquartile range (25^th– 75^th percentile), the horizontal line within the boxes represents the median, and the whisker bars extend to 1.5 times the interquartile range. Raw and log-transformed data are shown.</p