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Adriana Caroprezo Morini - One of the best experts on this subject based on the ideXlab platform.
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early transplantation of human immature dental pulp stem cells from baby teeth to Golden Retriever muscular dystrophy grmd dogs local or systemic
Journal of Translational Medicine, 2008Co-Authors: Irina Kerkis, Carlos Eduardo Ambrosio, Alexandre Kerkis, Daniele Dos Santos Martins, Eder Zucconi, Simone A S Fonseca, Rosa Cabral, Carlos Magno Da Costa Maranduba, Thais Peixoto Gaiad, Adriana Caroprezo MoriniAbstract:Background The Golden Retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression.
Daniel J. Bogan - One of the best experts on this subject based on the ideXlab platform.
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genetic myostatin decrease in the Golden Retriever muscular dystrophy model does not significantly affect the ubiquitin proteasome system despite enhancing the severity of disease
American Journal of Translational Research, 2014Co-Authors: Steven W Cotten, Daniel J. Bogan, Kristine M Wadosky, Cam Patterson, Monte S WillisAbstract:Recent studies suggest that inhibiting the protein myostatin, a negative regulator of skeletal muscle mass, may improve outcomes in patients with Duchenne muscular dystrophy by enhancing muscle mass. When the dystrophin-deficient Golden Retriever muscular dystrophy (GRMD) dog was bred with whippets having a heterozygous mutation for the myostatin gene, affected GRMD dogs with decreased myostatin (GRippets) demonstrated an accelerated physical decline compared to related affected GRMD dogs with full myostatin. To examine the role of the ubiquitin proteasome and calpain systems in this accelerated decline, we determined the expression of the muscle ubiquitin ligases MuRF1, Atrogin-1, RNF25, RNF11, and CHIP: the proteasome subunits PSMA6, PSMB4, and PSME1: and calpain 1/2 by real time PCR in the cranial sartorius and vastus lateralis muscles in control, affected GRMD, and GRippet dogs. While individual affected GRMD and GRippet dogs contributed to an increased variability seen in ubiquitin ligase expression, neither group was significantly different from the control group. The affected GRMD dogs demonstrated significant increases in caspase-like and trypsin-like activity in the cranial sartorius; however, all three proteasome activities in the GRippet muscles did not differ from controls. Increased variability in calpain 1 and calpain 2 expression and activity in the affected GRMD and GRippet groups were identified, but no statistical differences from the control group were seen. These studies suggest a role of myostatin in the disease progression of GRMD, which does not significantly involve key components of the ubiquitin proteasome and calpain systems involved in the protein quality control of sarcomere and other structural skeletal muscle proteins.
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The cranial sartorius muscle undergoes true hypertrophy in dogs with Golden Retriever muscular dystrophy.
Neuromuscular disorders : NMD, 2003Co-Authors: Diane D. Cundiff, Daniel J. Bogan, Janet R. Bogan, Carol S. OkamuraAbstract:Abstract The degree of atrophy or hypertrophy of selected pelvic limb muscles was determined in the canine homologue of Duchenne muscular dystrophy. While most muscles were atrophied, the caudal and cranial sartorius were hypertrophied. Cranial sartorius weights were corrected for body weight and endomysial space to determine true muscle weights (g/kg; mean±SD) in three Golden Retriever muscular dystrophy age groups, 4–10 (Group 1; n =15), 13–26 (Group 2; n =4), and 33–66 (Group 3; n =4) months and grouped normal dogs (6–20 months; n =12). Group 1 Golden Retriever muscular dystrophy weights (2.2063±0.6884) were greater than those of normal dogs (1.2699±0.1966), indicating that young Golden Retriever muscular dystrophy dogs have true cranial sartorius muscle hypertrophy. Values of Group 2 (1.3758±0.5078) and Group 3 (0.5720±0.2423) Golden Retriever muscular dystrophy dogs were less than those of Group 1, suggesting that the cranial sartorius muscle atrophies over time. Given that cranial sartorius muscle weight correlated with tarsal joint angle in affected dogs ( r =−0.817), the hypertrophied muscle may play a role analogous to iliotibial band tightness in Duchenne muscular dystrophy.
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contraction force generated by tarsal joint flexion and extension in dogs with Golden Retriever muscular dystrophy
Journal of the Neurological Sciences, 1999Co-Authors: Daniel J. Bogan, Janet R. Bogan, Martin K. Childers, Diane D. Cundiff, Gregory F. Petroski, Ronald O. SchuelerAbstract:Force generated due to torque caused by tarsal joint flexion and extension was measured noninvasively at 3, 4.5, 6, and 12 months of age in dogs with the Duchenne homologue, Golden Retriever muscular dystrophy (GRMD). Absolute and body-weight-corrected GRMD twitch and tetanic force values were lower than normal at all ages (P<0.01 for most). Tarsal flexion and extension were differentially affected. Flexion values were especially low at 3 months, whereas extension was affected more at later ages. Several other GRMD findings differed from normal. The twitch/tetany ratio was generally lower; post-tetanic potentiation for flexion values was less marked; and extension relaxation and contraction times were longer. The consistency of GRMD values was studied to determine which measurements will be most useful in evaluating treatment outcome. Standard deviation was proportionally greater for GRMD versus normal recordings. More consistent values were seen for tetany versus twitch and for flexion versus extension. Left and right limb tetanic flexion values did not differ in GRMD; extension values were more variable. These results suggest that measurement of tarsal tetanic force should be most useful to document therapeutic benefit in GRMD dogs.
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contraction tension and kinetics of the peroneus longus muscle in Golden Retriever muscular dystrophy
Journal of the Neurological Sciences, 1994Co-Authors: Nicholas J H Sharp, Daniel J. Bogan, Steven D Van Camp, Janet R Metcalf, Ronald O. SchuelerAbstract:Contraction tension and kinetics of the peroneus longus muscle were studied in dogs with the Duchenne homologue, Golden Retriever muscular dystrophy (GRMD), in advance of evaluating localized therapies such as myoblast transplantation. Absolute and both muscle- and body-weight-corrected twitch tension in GRMD dogs were low compared to normal litter mates at 3 months of age (p < 0.0005 for all). Tetanic tension was affected similarly. However, whereas absolute values were still reduced at 6 months (p < 0.0005 for twitch and 0.005 for tetany), twitch and tetanic tension corrected for either muscle or body weight was not statistically different, suggesting that the peroneus longus may be relatively spared in GRMD. Post-tetanic potentiation was more pronounced in GRMD versus normal dogs at both 3 (p < 0.0001) and 6 (p < 0.01) months. The degree of positive staircase at 3 months of age did not differ. Twitch contraction and relaxation times were dramatically prolonged, and there was concomitant sustained electrical activity, at, or before, 6 months of age in some severely affected dogs. Relatively few carriers were evaluated at these ages, but their values were similar to those of normal dogs. Apparent sparing of the peroneus longus muscle may limit application of this technique to evaluation of therapies administered early in life or in combination with toxins. Treatment to alter changes in contraction kinetics could also be assessed.
Robert B. Rebhun - One of the best experts on this subject based on the ideXlab platform.
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association of cancer related mortality age and gonadectomy in Golden Retriever dogs at a veterinary academic center 1989 2016
PLOS ONE, 2018Co-Authors: Michael S. Kent, Jenna H. Burton, Gillian Dank, Danika L. Bannasch, Robert B. RebhunAbstract:Golden Retriever dogs have been reported to have an increased prevalence of cancer compared to other breeds. There is also controversy over the effect spay or neuter status might have on longevity and the risk for developing cancer. The electronic medical records system at an academic center was searched for all dogs who had a necropsy exam from 1989-2016. 9,677 canine necropsy examinations were completed of which 655 were Golden Retrievers. Age was known for 652 with a median age of death 9.15 years. 424 of the 652 (65.0%) were determined to have died because of cancer. The median age for dying of a cause other than cancer was 6.93 years while those dying of cancer had a median age of 9.83 years (p<0.0001). There was no significant difference in the proportion of intact males and castrated males dying of cancer (p = 0.43) but a greater proportion of spayed females died of cancer compared to intact females (p = 0.001). Intact female dogs had shorter life spans than spayed female dogs (p<0.0001), but there were no differences between intact and castrated males. Intriguingly, being spayed or neutered did not affect the risk of a cancer related death but increasing age did. The most common histologic diagnosis found in Golden Retrievers dying of cancer was hemangiosarcoma (22.64%) followed by lymphoid neoplasia (18.40%). Overall Golden Retriever dogs have a substantial risk of cancer related mortality in a referral population and age appears to have a larger effect on cancer related mortality than reproductive status.
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Percent of Golden Retriever dogs dying of cancer and age of death over time.
2018Co-Authors: Michael S. Kent, Jenna H. Burton, Gillian Dank, Danika L. Bannasch, Robert B. RebhunAbstract:(A) Scatter plot with fitted regression line and 95% CI showing percent of Golden Retriever dogs undergoing necropsy exam that died from cancer by year. The results show a significant (P = 0.38, R2 = 0.16) but weak increase in the proportion of dogs with a cancer diagnosis over time. (B) Scatter plot with fitted regression line and 95% CI showing age of Golden Retriever dogs presenting for necropsy over time. The results show a significant but week increase in age over time (P = 0.01, R2 = 0.009).
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Age of Golden Retrievers broken out by sex and cause of death.
2018Co-Authors: Michael S. Kent, Jenna H. Burton, Gillian Dank, Danika L. Bannasch, Robert B. RebhunAbstract:Box and whisker plot showing median age, interquartile range, adjacent values and outliers of Golden Retriever dogs who underwent a necropsy exam and an attributable or non-attributable death from cancer categorized by sex and spay or neuter status. P values are shown for differences between cancer and non-cancer attributed deaths within each sex category and for differences between sex category within the cancer and non-cancer attributed death groups. NCAD = non-cancer attributable death, CAD = Cancer attributable death.
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Association of cancer-related mortality, age and gonadectomy in Golden Retriever dogs at a veterinary academic center (1989-2016)
2018Co-Authors: Michael S. Kent, Jenna H. Burton, Gillian Dank, Danika L. Bannasch, Robert B. RebhunAbstract:Golden Retriever dogs have been reported to have an increased prevalence of cancer compared to other breeds. There is also controversy over the effect spay or neuter status might have on longevity and the risk for developing cancer. The electronic medical records system at an academic center was searched for all dogs who had a necropsy exam from 1989–2016. 9,677 canine necropsy examinations were completed of which 655 were Golden Retrievers. Age was known for 652 with a median age of death 9.15 years. 424 of the 652 (65.0%) were determined to have died because of cancer. The median age for dying of a cause other than cancer was 6.93 years while those dying of cancer had a median age of 9.83 years (p
Ian J. Jackson - One of the best experts on this subject based on the ideXlab platform.
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melanocortin 1 receptor variation in the domestic dog
Mammalian Genome, 2000Co-Authors: Alison L Wilkie, Siobhan A Jordan, Danika L Metallinos, Lin He, N G Holmes, Ian J. JacksonAbstract:The melanocortin 1 receptor (Mc1r) is encoded by the Extension locus in many different mammals, where a loss-of-function causes exclusive production of red/yellow pheomelanin, and a constitutively activating mutation causes exclusive production of black/brown eumelanin. In the domestic dog, breeds with a wild-type E allele, e.g., the Doberman, can produce either pigment type, whereas breeds with the e allele, e.g., the Golden Retriever, produce exclusively yellow pigment. However, a black coat color in the Newfoundland and similar breeds is thought to be caused by an unusual allele of Agouti, which encodes the physiologic ligand for the Mc1r. Here we report that the predicted dog Mc1r is 317 residues in length and 96% identical to the fox Mc1r. Comparison of the Doberman, Newfoundland, Black Labrador, Yellow Labrador, Flat-coated Retriever, Irish Setter, and Golden Retriever revealed six sequence variants, of which two, S90G and R306ter, partially correlated with a black/brown coat and red/yellow coat, respectively. R306ter was found in the Yellow Labrador, Golden Retriever, and Irish Setter; the latter two had identical haplotypes but differed from the Yellow Labrador at three positions other than R306ter. In a larger survey of 194 dogs and 19 breeds, R306ter and a red/yellow coat were completely concordant except for the Red Chow. These results indicate that the e allele is caused by a common Mc1r loss-of-function mutation that either reoccurred or was subject to gene conversion during recent evolutionary history, and suggest that the allelic and locus relationships for dog coat color genes may be more analogous to those found in other mammals than previously thought.
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melanocortin 1 receptor variation in the domestic dog
Mammalian Genome, 2000Co-Authors: J M Newton, Alison L Wilkie, Siobhan A Jordan, Danika L Metallinos, Lin He, N G Holmes, Ian J. JacksonAbstract:The melanocortin 1 receptor (Mc1r) is encoded by the Extension locus in many different mammals, where a loss-of-function causes exclusive production of red/yellow pheomelanin, and a constitutively activating mutation causes exclusive production of black/brown eumelanin. In the domestic dog, breeds with a wild-type E allele, e.g., the Doberman, can produce either pigment type, whereas breeds with the e allele, e.g., the Golden Retriever, produce exclusively yellow pigment. However, a black coat color in the Newfoundland and similar breeds is thought to be caused by an unusual allele of Agouti, which encodes the physiologic ligand for the Mc1r. Here we report that the predicted dog Mc1r is 317 residues in length and 96% identical to the fox Mc1r. Comparison of the Doberman, Newfoundland, Black Labrador, Yellow Labrador, Flat-coated Retriever, Irish Setter, and Golden Retriever revealed six sequence variants, of which two, S90G and R306ter, partially correlated with a black/brown coat and red/yellow coat, respectively. R306ter was found in the Yellow Labrador, Golden Retriever, and Irish Setter; the latter two had identical haplotypes but differed from the Yellow Labrador at three positions other than R306ter. In a larger survey of 194 dogs and 19 breeds, R306ter and a red/yellow coat were completely concordant except for the Red Chow. These results indicate that the e allele is caused by a common Mc1r loss-of-function mutation that either reoccurred or was subject to gene conversion during recent evolutionary history, and suggest that the allelic and locus relationships for dog coat color genes may be more analogous to those found in other mammals than previously thought.
Irina Kerkis - One of the best experts on this subject based on the ideXlab platform.
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early transplantation of human immature dental pulp stem cells from baby teeth to Golden Retriever muscular dystrophy grmd dogs local or systemic
Journal of Translational Medicine, 2008Co-Authors: Irina Kerkis, Carlos Eduardo Ambrosio, Alexandre Kerkis, Daniele Dos Santos Martins, Eder Zucconi, Simone A S Fonseca, Rosa Cabral, Carlos Magno Da Costa Maranduba, Thais Peixoto Gaiad, Adriana Caroprezo MoriniAbstract:Background The Golden Retriever muscular dystrophy (GRMD) dogs represent the best available animal model for therapeutic trials aiming at the future treatment of human Duchenne muscular dystrophy (DMD). We have obtained a rare litter of six GRMD dogs (3 males and 3 females) born from an affected male and a carrier female which were submitted to a therapeutic trial with adult human stem cells to investigate their capacity to engraft into dogs muscles by local as compared to systemic injection without any immunosuppression.