Journal Articles

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    A novel frameshift variant in ALS2 associated with segmental axonopathy in Merino sheep
    (BioMed Central Ltd, 2025-12-01) Eager KLM; Jolly RD; Manning L; Willet CE; Snell RG; Lehnert K; Mckean NE; Sneddon NW; O’Rourke BA; Dittmer KE; Tammen I; Littlejohn M
    Background: Segmental axonopathy is a recessively inherited neurodegenerative disorder that has affected Merino sheep since the early 1930s. Despite its long-standing recognition, the genetic basis of the condition remained unknown. This study aimed to identify the genetic cause of segmental axonopathy and confirm its pathological features to improve diagnostic accuracy and inform breeding strategies. Results: Whole genome sequencing and genotyping of affected and unaffected Merino sheep identified a novel homozygous frameshift variant in the ALS2 gene that segregated with disease. RNA sequencing of cerebellar peduncle tissue confirmed the nonsense consequence on the ALS2 transcript. Histological analysis highlighted the hallmarks of the disease as large, foamy eosinophilic axonal swellings predominantly in the trigeminal ganglia, with additional degenerative changes in both the brain and spinal cord. These findings support the value of targeted sampling of sensory roots of the trigeminal nerve, spinal cord tracts, and dorsal nerve rootlets to enhance diagnostic accuracy. The same ALS2 variant was found across multiple unrelated flocks in both Australia and New Zealand, indicating a broader presence within the fine-wool Merino sheep population. Conclusions: This study identifies a novel ALS2 frameshift variant associated with segmental axonopathy in Merino sheep and provides both genetic and histological evidence supporting its role in disease pathology. The development of a DNA diagnostic test will enable more informed breeding decisions, reduce the prevalence of this condition, and improve animal welfare and productivity in the Merino industry. Moreover, the findings offer a potential large-animal model for exploring early-onset forms of human motor neuron diseases, including amyotrophic lateral sclerosis, in which ALS2 variants are implicated.
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    Insights into the pathogenesis of catastrophic spontaneous humeral fractures in first-lactation dairy cows
    (CSIRO Publishing, Australia, 2025-05-06) Wehrle-Martinez AS; Lawrence KE; Back PJ; Rogers CW; Gibson MJ; Dittmer KE; Eastwood C
    Spontaneous humeral fractures in first-lactation dairy cows have introduced significant challenges to the dairy industry in New Zealand, impacting animal welfare, farm economics, and veterinary practices. This review synthesizes current knowledge on the pathogenesis of these fractures and identifies potential key risk factors. The majority of bones from affected first-lactation dairy cows have osteoporosis, which is associated with inadequate bone formation and increased bone resorption. In addition, low total collagen content in bones from most affected dairy cows supports the hypothesis that inadequate bone formation is an important risk factor associated with humeral fractures in these cows. Spectroscopic analyses further confirmed a significant reduction in bone quality and strength. Novel findings suggest that low liver copper concentration in many of the affected cows' results from the mobilisation of copper to the bone. Although limited, the accumulated evidence suggests that to mitigate the incidence of catastrophic fractures, adequate nutrition (especially protein-energy) should be supplied during important growth periods. While significant progress has been made in understanding the cause of these fractures, many uncertainties and areas requiring further research remain.
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    The Relationship Between Stature and Live Weight of Dairy Cows Between Birth and Maturity
    (MDPI (Base, Switzerland), 2025-03) Gibson MJ; Sneddon NW; Rogers CW; Back PJ; Dittmer KE; Martín NP; Bezerra LR; Lancaster P
    Lactational and reproductive performance are strongly associated with cow live weight and capacity. However, there are limited data published describing capacity (thoracic) growth and the prediction of final stature and capacity from measurements at birth. Therefore, the aim of this study was to examine the relationship between stature and live weight of female dairy cattle between birth and maturity. Forty dairy cows, with records of stature and capacity from birth up until two years of age, underwent follow-up measurements for live weight, height at withers, wither-rump length, girth circumference and leg length on four occasions between 42 and 52 months of age. Measures of wither height, leg length and wither rump length at fourth mating had the strongest association with measures at birth (R2 > 0.90) compared to girth and live weight (R2 = 0.88 and 0.82, respectively). The weaker association between birth and maturity measures for girth is likely a reflection of the stronger relationship with live weight resulting in a later maturity (approximately 810 days) compared to linear measures such as height (approximately 730 days). Therefore, to maximise capacity, adequate nutrition is required until approximately 810 days of age when capacity growth is most sensitive to environmental input.
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    The association between fluoride concentrations and spontaneous humeral fracture in first-lactation dairy cows: results from two New Zealand studies
    (Taylor and Francis Group, 2024-11-17) Wehrle-Martinez A; Dittmer KE; Back PJ; Rogers CW; Weston JF; Jeyakumar P; Pereira RV; Poppenga R; Taylor HS; Lawrence KE
    AIM: To assess whether the fluoride concentration in the humeri of first-lactation, 2-year-old dairy cows with a spontaneous humeral fracture is significantly different from that of first-lactation, 2-year-old dairy cows without a humeral fracture. METHODS: Two studies were conducted, the first with nine bone samples from 2-year-old, first-calving dairy cows with a humeral fracture (all from the Waikato region) age-matched with seven control bone samples from the Waikato, Bay of Plenty and Manawatū-Whanganui regions. The second study used 26 bone samples from 2-year-old, first-lactation dairy cows with a humeral fracture (from the Otago, Canterbury, Southland, West Coast, Waikato and Manawatū-Whanganui regions) age-matched with 14 control bone samples (all from the Manawatū-Whanganui region or unknown). Control bone samples were from first-lactation, 2-year-old dairy cows that did not have humeral fractures. Bone fluoride concentration was quantified for all samples. RESULTS: The median fluoride concentration of humeri from first-lactation, 2-year-old dairy cows with a humeral fracture was significantly higher than humeri from unaffected control cows in both studies. In Study 1, the median bone fluoride concentration was 599 (IQR 562.7-763.5) mg/kg from case cows and 296.6 (IQR: 191.2-391.7) mg/kg from control cows (p < 0.001), and in Study 2 the median bone fluoride concentration from case and control cows was 415 (IQR: 312.5-515) mg/kg and 290 (IQR: 262.5-410) mg/kg (p = 0.04) respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Although there are limitations to this study due to the unbalanced regional distribution of cases and controls, the results indicate that sub-clinical fluoride toxicosis may be linked to spontaneous humeral fractures in first-lactation dairy cows in New Zealand. Further research is required to determine if bone fluoride concentrations play a role in the pathogenesis of these fractures.
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    The intrauterine effects of a maternal winter diet of either kale or fodder beet on measures of calf stature and bone morphology at birth
    (Taylor and Francis Group, 2024-10-09) Gibson MJ; Rogers CW; Back PJ; Dittmer KE; Wehrle-Martinez A; Dalley DE; Woods RR
    Fodder beet and kale are commonly used winter crops in New Zealand dairy and dairy support farm systems. Fodder beet (FB) is known to have lower crude protein, phosphorus and calcium content compared to kale. The intrauterine effects of feeding FB during late pregnancy on bone growth and development in calves requires attention. This study aimed to examine the intrauterine effects of a maternal diet of either kale or FB on measures of calf stature and bone morphology at birth. In winters 2019 and 2020, two herds of pregnant Friesian ×Jersey cows were fed either kale (2019, 2020 n = 20) or FB (2019, 2020 n = 20) supplemented with pasture baleage. Calves born from these mobs were euthanised within ten days of birth and a forelimb and section of rib including the costochondral junction were harvested for peripheral quantitative computed tomography and histological analysis. Calves from the FB treatment had reduced bone density and strength compared to calves from the kale treatment (p <.05). The effect of a nutritional deficit on bone morphology at birth emphasises the importance of sufficient nutrition in pre-calving diets. Future research is required to examine the long-term impact of dam undernutrition on calf growth and production.
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    Farm management and husbandry practices associated with spontaneous humeral fractures in New Zealand dairy heifers.
    (Taylor and Francis Group, 2024-02-04) Wehrle-Martinez A; Lawrence KE; Back PJ; Rogers CW; Dittmer KE
    AIMS: To use a farm-based survey to identify characteristics of the New Zealand dairy system associated with the risk of spontaneous humeral fracture in dairy heifers. METHODS: A questionnaire was designed and made available in print and online to collect information from dairy farmers and/or veterinarians, across New Zealand, about the management and nutrition of cows from birth to first lactation. Data were collected from July 2019 to March 2020 from farms that either had recorded (case farms) or not recorded (control farms) cases of humeral fractures in dairy heifers. RESULTS: A total of 68 completed questionnaires were returned, with 35 responses from case farms and 33 responses from control farms. Twenty-six responses (38%) were from the South Island (13 case farms and 13 control farms) and 38 responses (56%) were from the North Island (20 case farms and 18 control farms). For four questionnaires (6%) farm location was not given. Adjusting for the effect of age when calves accessed pasture, case farms had increased odds of having Holstein-Friesian Jersey crossbreed cows as the predominant breed (OR = 9.7; 95% CI = 3.1-36.0; p < 0.001). Adjusting for the effect of breed, allowing calves access to pasture a week later decreased the odds of being a case farm (OR = 0.68; 95% CI = 0.47-0.90; p = 0.006). CONCLUSIONS: Cows being Holstein-Friesian Jersey crossbreed was identified as a possible risk factor associated with spontaneous humeral fracture in dairy heifers in New Zealand. Given the small sample size, the likely multifactorial aetiology for humeral fractures, and the non-randomised survey, this risk factor, and the possible association between age at turn out and herd production with humeral fractures, all require further investigation.
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    Debilitating Musculoskeletal Disease in Two Free-Ranging Juvenile American Black Bears (Ursus americanus).
    (MDPI (Basel, Switzerland), 2024-07-17) Fahrenholz IC; Dennis MM; Morandi F; Dittmer KE; Sheldon JD; Gottdenker N; Tinelli A
    Severe musculoskeletal disease characterized by marked joint laxity was the cause of euthanasia in two wild juvenile American black bears (Ursus americanus) admitted to a rehabilitation facility in eastern Tennessee in 2023. Previously, almost all reported musculoskeletal diseases in this population were of traumatic etiology, even in malnourished yearlings. Case 1 was an orphaned 11-month-old male cub exhibiting disproportionate dwarfism, progressive immobility, and joint laxity. Necropsy findings suggested either chondrodysplasia or rickets, and imaging findings supported a skeletal dysplasia. Case 2 was a 14-month-old emaciated male yearling exhibiting joint laxity and immobility. Necropsy findings showed osteoporosis and serous atrophy of fat, and imaging findings were inconsistent with a skeletal dysplasia. Both cases were clinically inconsistent with rickets based on normal calcium, phosphorous, and parathyroid hormone concentrations; however, Case 1 had hypovitaminosis D (9 nmol/L) compared to healthy juvenile black bears. We hypothesize that Case 1 had a genetic chondrodysplasia while the osteoporosis of Case 2 was due to chronic malnutrition. The goal of this case report is to inform wildlife agencies and facilities to monitor for similar, non-trauma-related debilitating musculoskeletal disease in free-ranging bears and evaluate cases that allow us to further understand the disease processes involved.
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    Enzootic calcinosis in Toggenburg goats in New Zealand.
    (Taylor and Francis Group, 2024-01-01) Brown SE; Collett MG; Matthews ZM; Marshall JC; Dittmer KE
    CASE HISTORY: Necropsies on Toggenburg goats culled from a small farm in the Manawatū district of New Zealand, performed at Massey University (Palmerston North, NZ) over a period of 29 years (1991-2019), revealed soft tissue mineralisation, particularly of cardiovascular tissues. The farm spans 10 acres and runs between 15 and 30 Toggenburg goats. The goats are predominantly on pasture comprising a variety of types. PATHOLOGICAL FINDINGS: Necropsies were performed on all adult goats (n = 45) that died or were euthanised. Histopathology was performed on 42 goats (93%), of which 33 (73%) included sufficient tissues diagnostically relevant to soft tissue mineralisation. The most significant gross findings were in various arteries, with the aorta most commonly affected, followed by the heart and lungs. The aortic intima showed prominent, multifocal to coalescing, raised, wrinkled, white plaques. Microscopically there were multiphasic lesions of mineralisation, chondroid, and osseous metaplasia in the elastic arteries, aorta, heart and lungs. A lumbar vertebra from one goat had prominent, basophilic, fibrillar, tangled matrix lining Haversian canals and lamellae. LABORATORY FINDINGS: Blood samples were collected from 15 adult goats in the affected herd and from 10 adult Toggenburg goats from an unaffected herd. Samples were collected by jugular venipuncture at 2-month intervals for 12 months (April 2018-March 2019). Concentrations of calcium, phosphorus, 25-hydroxyvitamin D2 and D3 (25OHD2, 25OHD3) in serum were analysed. The concentration of total 25OHD in serum was 34.2 (95% CI = 18.9-49.4) nmol/L (p < 0.001) higher in goats from the affected herd than in goats from the unaffected herd. Serum 25OHD2 concentration was 46.2 (95% CI = 39.2-53.2) nmol/L higher (p < 0.001) in goats from the affected herd compared to the unaffected herd. Serum Ca concentrations in affected goats were 0.101 (95% CI = 0.005-0.196) mmol/L higher (p = 0.039) than unaffected goats, but remained within the reference range. There was no evidence of a difference in serum 25OHD3 and P concentration between the herds. VEGETATION SURVEY: All paddocks on the property were surveyed every 2 months along evenly spaced line transects, and then further traversed perpendicularly to form a grid. No known calcinogenic species were identified. Known plant sources of vitamin D identified on the farm included mushrooms (species not defined), Dactylis glomerata, lichen, pine pollen, and algae. DIAGNOSIS: Soft tissue mineralisation and enzootic calcinosis. CLINICAL RELEVANCE: Veterinarians are alerted to the possibility of either enzootic calcinosis in goats and the potential occurrence of calcinogenic plants in New Zealand; or chronic vitamin D toxicosis of non-plant origin.
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    Endocrine fibroblast growth factors in domestic animals.
    (Elsevier B.V., 2024-07-09) Brinker EJ; Hardcastle MR; Dittmer KE; Graff EC
    Fibroblast growth factors (FGFs) are a group of structurally homologous yet functionally pleiotropic proteins. Canonical and intracellular FGFs have primarily autocrine or paracrine effects. However, the FGF19 subfamily, composed of FGF15/19, FGF21, and FGF23, act as endocrine hormones that regulate bile acid, metabolic, and phosphorus homeostasis, respectively. Current research in human and rodent models demonstrates the potential of these endocrine FGFs to target various diseases, including disorders of inherited hypophosphatemia, chronic liver disease, obesity, and insulin resistance. Many diseases targeted for therapeutic use in humans have pathophysiological overlaps in domestic animals. Despite the potential clinical and economic impact, little is known about endocrine FGFs and their signaling pathways in major domestic animal species compared with humans and laboratory animals. This review aims to describe the physiology of these endocrine FGFs, discuss their current therapeutic use, and summarize the contemporary literature regarding endocrine FGFs in domestic animals, focusing on potential future directions.
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    Multimodal Blockade of the Renin-Angiotensin System in the Treatment of Cancer in Dogs Has Mild Adverse Effects in Some Dogs.
    (MDPI (Basel, Switzerland), 2024-06-17) Dittmer KE; Wetzel S; Odom T; Munday JS; Flatt EA; Wilson IJ; Hughes C; Tan ST; Ferreira F; Sparger EE
    The renin-angiotensin system (RAS) is increasingly being recognized to play a role in the tumor microenvironment, promoting tumor growth. Studies blocking a single part of the RAS have shown mixed results, possibly due to the existence of different bypass pathways and redundancy within the RAS. As such, multimodal blockade of the RAS has been developed to exert more complete inhibition of the RAS. The aim of the present study was to assess the safety of multimodal RAS blockade in dogs. Five dogs (four with appendicular osteosarcoma, one with oral malignant melanoma) were treated with atenolol, benazepril, curcumin, meloxicam, and metformin. The dogs underwent clinical examination, blood pressure measurement, and hematology and serum biochemistry tests performed at 0, 1, 3, 6, 9, and 12 weeks, then every 3 months thereafter. End-of-life decisions were made by the owners. None of the dogs developed hypotension. One dog had intermittent vomiting during the 64 weeks it was on the trial. One dog had a one-off increase in serum SDMA(symmetrical dimethylarginine) concentration. Dogs were euthanized at weeks 3 (osteosarcoma), 10 (osteosarcoma), 17 (osteosarcoma), and 26 (oral malignant melanoma), and one dog was still alive at the end of the trial at 64 weeks (osteosarcoma). This is the first assessment of multimodal blockade of the RAS in dogs, and the results suggest it causes only mild adverse effects in some animals. The efficacy of the treatment was not assessed due to the small number of dogs. This pilot study allows for future larger studies assessing multimodal RAS blockade for the treatment of canine cancer.