The Rat Genome Database (RGD) facilitates genomic and phenotypic data integration across multiple species for biomedical research.

Model organism research is essential for discovering the mechanisms of human diseases by defining biologically meaningful gene to disease relationships. The Rat Genome Database (RGD, ( https://rgd.mcw.edu )) is a cross-species knowledgebase and the premier online resource for rat genetic and physiologic data. This rich resource is enhanced by the inclusion and integration of comparative data for human and mouse, as well as other human disease models including chinchilla, dog, bonobo, pig, 13-lined ground squirrel, green monkey, and naked mole-rat. Functional information has been added to records via the assignment of annotations based on sequence similarity to human, rat, and mouse genes. RGD has also imported well-supported cross-species data from external resources. To enable use of these data, RGD has developed a robust infrastructure of standardized ontologies, data formats, and disease- and species-centric portals, complemented with a suite of innovative tools for discovery and analysis. Using examples of single-gene and polygenic human diseases, we illustrate how data from multiple species can help to identify or confirm a gene as involved in a disease and to identify model organisms that can be studied to understand the pathophysiology of a gene or pathway. The ultimate aim of this report is to demonstrate the utility of RGD not only as the core resource for the rat research community but also as a source of bioinformatic tools to support a wider audience, empowering the search for appropriate models for human afflictions.

Comparison of standardbred trotters exercising on a treadmill and a race track with identical draught resistances.

The responses in heart rate, plasma lactate and rectal temperature of standardbred trotters to draught loaded interval exercise on a treadmill and a race track were studied. The horses were exercised with incrementally increasing trotting speeds for two-minute intervals with draught loads of 10, 20 and 30 kilopond (kp) in three different tests. Each trotting interval was followed by two-minute periods at a walk without a draught load. Measurements of heart rate and plasma lactate were made at the end of each interval and the rectal temperature was taken at the end of the exercise. The heart rate and plasma lactate levels were significantly lower on the treadmill than on the track in the tests with 10 kp, but no significant differences were found between the treadmill and track exercise tests with the heavier draught resistances. No differences were observed in rectal temperature between treadmill and track conditions. From these findings it was concluded that the workload was significantly greater on the race track compared to the treadmill when the draught resistance was low (10 kp). Although the workload increased on both the race track and the treadmill as draught resistance increased, at the heavier draught resistances track exercise was no longer more demanding than exercise on the treadmill.

Exercise response, metabolism at rest and digestibility in athletic horses fed high-fat oats.

REASON FOR PERFORMING STUDY: High starch intakes increase the risk for metabolic disorders and therefore alternative feedstuffs are of interest. High-fat oat varieties have a lower starch and higher energy content than regular oats and may therefore be useful in this context. HYPOTHESIS: Feeding high fat oats causes no adverse effects on the response to exercise and that the total amount of oats offered could be reduced compared to feeding with regular oats. METHODS: Twelve Standardbred trotters were fed regular oats (diet C), high-fat oats (F), and a mixture (50:50) of C and F (M), together with haylage (30:70), in a Latin square design trial. High-fat oats replaced regular oats in a 0.9 to 1.0 ratio in diets F and M. On Day 18 in each 21 day experimental period, horses were subjected to a standardised near-maximal treadmill exercise test with collection of blood samples and muscle biopsies before and after exercise. This was followed by a 3 day period of total collection of faeces and urine. RESULTS: There were no significant effects of dietary treatments on bodyweight, heart rate, plasma lactate and glucose, or on muscle glycogen and lactate concentrations following exercise. However, plasma insulin was reduced during exercise on diets F and M compared to diet C. The total tract digestibility of dry matter, fat, protein, NDF and organic matter were higher for diet F than for diet C. CONCLUSION: High-fat oats can replace regular oats in the diet of athletic horses without any adverse effects on metabolism and exercise response. POTENTIAL RELEVANCE: Due to the high energy content and a high digestibility of dietary components in high-fat oats the daily allowance of oats can be reduced and thus the intake of starch.

The opioid haemorphin-7 in horses during low-speed and high-speed treadmill exercise to fatigue.

The opioid neuropeptide haemorphin-7 was measured, by immunoreactivity, in Standardbred horses during low-speed (7 m/s) and high-speed (10 m/s) endurance exercises, lasting 49-58 and 12-16 min respectively. In parallel, heart rate, muscle temperature and plasma lactate concentrations were measured. The profile of the low-speed exercise showed significantly increased heart rate after 10 min [154 beats per minute (bpm)]. After the exercise, muscle temperature (42.1 degrees C) and plasma lactate (4.8 mmol/l) were significantly increased. The profile of the high-speed exercise was comparatively characterized by a higher increase of heart rate after 5 min (194 bpm) and higher increases of muscle temperature (43.2 degrees C) and lactate levels (15.8 mmol/l) after the exercise. The horses were probably exhausted by glycogen depletion in the low-speed exercise and by muscle pH decrease in the high-speed exercise. Haemorphin-7 increased significantly during the high-speed exercise (274.8 fmol/ml) but not during low speed (108.3 fmol/ml), coincident with the results of lactate. These results suggest that plasma haemorphin-7 is measurable in the horse by immunoreactivity, and that intense exercise stimulates release of this opioid. Such endogenous opioids are most likely involved in regulatory functions associated with pain, physical effort, inflammation, and blood pressure variation in horses, as have been established in other species.

Elemental composition of muscle at rest and potassium levels in muscle, plasma and sweat of horses exercising at 20 degrees C and 35 degrees C.

In this study, 4 Standardbred geldings were exercised at 20 and 35 degrees C. The exercise test (ET) consisted of 2 exercise bouts separated by 2 h of rest in their boxes. Blood samples were taken before, during and after the second exercise bout and muscle (m. gluteus medius) biopsies were taken before the first exercise bout and after an intensive trot over 2600 m in the second exercise bout. The blood samples were analysed for plasma potassium and total plasma protein concentration (TPP) and the muscle fibres were analysed for elemental composition by x-ray microanalysis. The intracellular content was as follows: sodium (Na) = 40 +/- 7; magnesium (Mg) = 32 +/- 4; phosphorus (P) = 282 +/- 15; sulphur (S) = 222 +/- 13; chloride (Cl) = 119 +/- 31; potassium (K) = 304 +/- 21 and calcium (Ca) = 8 +/- 2 mmol/kg dry weight under resting conditions. Intracellular potassium content increased after exercise compared to resting values. There was a good correlation between exercise intensity, plasma potassium concentration and shifts in plasma volume, indicated by alterations in TPP. This probably reflects the very fast shift of potassium and fluid between muscle and plasma. Plasma potassium concentrations decreased below resting values post exercise. The higher dehydration degree and potassium sweat loss after exercise at 35 degrees C was not reflected in lower muscular potassium content, but by a lower plasma potassium/total plasma protein ratio after exercise, indicating less circulating potassium.

Cardio-respiratory and plasma lactate responses to exercise with low draught resistances in standardbred trotters.

Five Standardbred trotters performed treadmill exercise with incrementally increasing trotting velocities for 2 min intervals in three different tests until fatigue. Each test was performed with draught loads of either 10, 20 or 30 kilopond (kp). Each trotting interval was followed by 2 min periods at a walk without draught load. Recordings were made of heart rate (HR), respiratory rate (RR), plasma lactate (PLA) and stride frequency (SF) at the end of each trotting interval. The HR increased to average values of 191 +/- 10,203 +/- 10 and 214 +/- 7 bpm and PLA increased to 3.8 +/- 0.7, 7.3 +/- 3.8 and 10.8 +/- 6.4 mmol/l at 9 m/s in the three tests, respectively. The HR response to exercise was significantly higher with increasing draught loads, and PLA was significantly higher with 30 kp compared to 10 kp draught resistance. The lowest respiratory rate was seen in the test with 30 kp loading. Peak oxygen uptake (VO2peak) was measured in a separate test on a sloped treadmill with increasing velocities without draught load and averaged 70.4 +/- 9.11/min. Muscle biopsies were taken from the gluteus muscle. Individual variations were seen in VO2peak, muscle fibre composition and HR and PLA responses to exercise. In conclusion, at a certain velocity a small increase in draught resistance from 10 to 30 kp significantly increases both the HR and PLA responses. At comparable work intensities the horses differed in circulatory and metabolic responses to exercise.

Cardiovascular, respiratory and metabolic effects of interval training at VLA4.

The purpose of this study was to determine if training with short intervals at the velocity producing a lactate level of 4 mmol/l (VLA4) is sufficient to induce adaptations and better exercise tolerance. Five Standardbred mares (4-8 years) were interval trained on a treadmill 3 days a week for 12 weeks and subsequently detrained for 4 weeks. Standardized exercise tests were performed before, during and after the training period and muscle biopsies were taken. Measurements were made of heart rate, oxygen consumption, stride frequency, blood volume and blood lactate. Plasma volume was reduced after 2 weeks of training but then increased to the approximate pre-training value throughout the remaining training and post-training periods. No change was detected in the total cell volume whereas the total blood volume varied in consequence with the plasma volume variation. A significant reduction in heart rate response to exercise was seen after 4 weeks of training. VLA4 increased after 2 weeks of training and remained higher than the baseline value during the rest of the training period. Consequently, the blood lactate at 8 m/sec was decreased compared to baseline concentration after 8 and 12 weeks of training. The post-training VLA4 did not differ significantly either from the end of training or from the pre-training value. Mass specific oxygen consumption (VO2-200/BW) at V200 increased with training and decreased with detraining. The respiratory quotient at a velocity of 8 m/sec decreased from 1.18 +/- 0.02 before training to 1.07 +/- 0.02 (P < 0.05) at the end of training. No changes were found in muscle histo- or biochemical parameters. The results indicate that training at VLA4 is sufficient to cause adaptational changes in exercise tolerance related parameters.

The kinematics of loading and fatigue in the standardbred trotter.

The Standardbred trotter must pull a considerable load when racing and, consequently, draught loading is a common method of training in the Standardbred and the effects of loading and fatigue due to loading on the locomotor pattern was the purpose of this investigation. Four mature healthy Standardbred horses trotted with and without a horizontal-pulling loading of 34 kg until the horses were no longer willing to keep pace with the treadmill despite encouragement. Heart rate was monitored every min using a bipolar electrocardiogram. The kinematics for 5 consecutive strides were filmed. Horses exercised on the treadmill for 7-10 mins. The mean heart rate was 206 beats/min at the end of the exercise. Due to draught loading, the horses reduced significantly the time of the stance phase in both the fore- and hindlimb. Three of the 4 horses reduced their stride lengths as the result of increased loading. The general movement pattern of the horses remained similar. More dramatic changes in the movement pattern were observed because of fatigue. The limbs of the horse were significantly more compressed as the result of greater joint excursion during the stance phase. Furthermore, the length of stride was significantly increased as the result of fatigue. The results show that both loading and fatigue change the locomotor pattern of the Standardbred trotter. Although the horizontal loading was considerable, the horse maintained similar joint movement with increases in stride frequency. During fatigue the horse seems to be unable to maintain stride frequency, probably due to a compromised power capacity of the muscles. The increase in joint excursion due to fatigue may have an important influence on certain types of injury to the locomotor system of the racehorse.

Muscle adenine nucleotide degradation during submaximal treadmill exercise to fatigue.

The aim was to investigate metabolic response in muscle during submaximal treadmill exercise to fatigue, with a special emphasis on adenine nucleotide degradation products such as inosine monophosphate (IMP) in muscle and hypoxanthine, xanthine and uric acid in plasma. Five Standardbred trotters performed treadmill exercise on 2 occasions, once at 7 m/s and once at 10 m/s. Venous blood samples were taken at rest, during exercise and at the end of exercise. Muscle biopsies were taken before and after exercise and muscle temperature was measured before and after exercise. Running time differed among horses and was 48-58 min at 7 m/s and 10-15.5 min at 10 m/s. Both lactate and uric acid concentrations in plasma showed a gradual increase during exercise at both 7 and 10 m/s. At the end of exercise, values for uric acid were higher and values for lactate lower at 7 m/s compared with at 10 m/s. No marked changes were seen in plasma concentrations of hypoxanthine or xanthine with exercise. Muscle glycogen decreased after exercise at both 7 and 10 m/s with a marked depletion seen in some fibres. Muscle lactate concentrations increased after exercise at both 7 m/s and at 10 m/s. No significant changes were seen in adenosine triphosphate (ATP), ADP and AMP concentrations, whereas IMP concentrations increased after exercise at both 7 m/s and at 10 m/s. The results of this study indicate that AMP deamination occurs with submaximal exercise and that development of fatigue may be related to adenine nucleotide degradation in muscle.

A comparison of the ultrastructure and metabolic response of the skeletal muscle of horses performing intense treadmill exercise at 20 and 35 degrees C.

The aim of this study was to determine whether the metabolic response and ultrastructure of muscle differed when horses performed intense exercise at different ambient temperatures. Four Standardbred geldings performed treadmill exercise, including an intensive trot of 2600 m on two different occasions, either at a high ambient temperature of 35 degrees C or at a temperature of 20 degrees C. The horses had a warm-up period of 23.5 min of submaximal exercise, followed by 2 h of box rest before the intensive exercise. Muscle biopsy data of adenine nucleotides, creatine phosphate, lactate and glycogen concentrations measured before the warm-up period were similar to those measured before the period of intensive exercise. Muscle lactate concentrations did not differ between the two temperatures, but increased significantly after intense exercise to levels of 34.7 +/- 8.3 mmol/kg d.w. at 20 degrees C, and to 41.7 +/- 12.5 mmol/kg d.w. at 35 degrees C. Muscle glycogen and creatine phosphate concentrations did not differ between the two ambient temperatures, but decreased significantly by 122 +/- 82 mmol/kg d.w. and 25.2 +/- 17.4 mmol/kg d.w., respectively, after the intensive exercise. No changes were seen in adenosine triphosphate, adenosine diphosphate and adenosine monophosphate concentrations. The muscle biopsies were investigated by electron microscopy, and showed no marked changes in the ultrastructure of the muscle due to exercise at the two different ambient temperatures. In conclusion, no marked changes were seen in the muscle metabolic response or in the ultrastructure of the muscle when the horses performed intense exercise at 35 degrees C compared to 20 degrees C.