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C-C chemokine receptor 7 (CCR7) contributes to cell homing to lymph nodes (LNs). Recent studies reported that CCR7 is also expressed in tumor cells, which correlates with LN metastasis in various cancers. However, the expression of CCR7 in tumor cells is unknown in dogs due to the lack of appropriate antibodies. In the present study, a fusion protein of C-C chemokine ligand 19 (CCL19) was employed as an alternative method to CCR7 antibodies. The fusion CCL19 protein specifically detected CCR7 expressed in canine lymphoma cell lines, which showed active chemotaxis to both canine and mouse ligands. The present study will help further research on the involvement of canine CCR7 in LN metastasis.

Canine degenerative myelopathy (DM) is a progressive neurodegenerative disease of the spinal cord. The diagnosis is based on the observation of clinical signs, genetic testing, and exclusion of other spinal cord diseases, and a definitive diagnosis of DM can only be confirmed by postmortem histopathological findings. The aim of this study was to investigate the diagnostic ability of diffusion tensor imaging (DTI) for DM. Eight DM-affected Pembroke Welsh Corgis, thirteen dogs with thoracolumbar intervertebral disk herniation (IVDH), and six healthy control dogs were included. All dogs were scanned using a 3.0-T MRI system. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were calculated for each intervertebral disk level slice between T8-T9 and L2-L3 intervertebral disk levels, and the entire area of the thoracolumbar spinal cord between T8-T9 and L2-L3 intervertebral disk levels (T8-L3 region). The ADC and FA values of the T8-L3 region were significantly lower in the DM group than in the IVDH group. The ADC values for the T8-L3 region had a moderate negative correlation with clinical duration (r

In human erythema multiforme (EM), cytotoxic T lymphocytes (CTLs) play an essential role in the pathogenesis. In canine EM, immunohistochemical staining with anti-CD8 antibody using frozen sections has shown the involvement of CTLs; however, CTL infiltration has never been quantitatively analyzed. We herein quantitatively analyzed CTL infiltration by immunohistochemical staining with granzyme B and CD3 antibodies using paraffin sections of a dog with EM associated with zonisamide. The present results indicated approximately 70% of cells at the border between the epidermis and dermis consisted of CTLs. Detection of granzyme B and CD3 using paraffin sections employed in this study can be a clinically applicable method for detecting CTLs.

A 17-year-old mongrel dog and 12-year-old Shiba Inu dog presented with ataxia and paresis of the pelvic limbs, respectively. Gas accumulation within the spinal canal adjacent to the herniated disc was suspected in both cases. Since the gas remained accumulated for a prolonged period, hemilaminectomy was performed to decompress the spinal cord. The bulged external lamina of the dura matter was removed and histopathologically examined. Granulomatous inflammation and hyperplasia of fibrous connective tissues was noted, suggesting that the gas was encapsulated and the fibrous nodules made reabsorption difficult. Clinical signs resolved post-surgery. This is the first report describing histopathological features of pneumorrhachis in dogs. The accumulated gas was successfully removed by surgery. Postoperative course remained uneventful in both cases.

OBJECTIVE To measure expression of microRNAs (miRNAs) in plasma and in extracellular vesicles (EVs) derived from plasma for dogs with glioma and dogs with other brain diseases. SAMPLE Plasma samples from 11 dogs with glioma and 19 control dogs with various other brain diseases. PROCEDURES EVs were isolated from plasma samples by means of ultracentrifugation. Expression of 4 candidate reference miRNAs (let-7a, miR-16, miR-26a, and miR-103) and 4 candidate target miRNAs (miR-15b, miR-21, miR-155, and miR-342-3p) was quantified with reverse transcription PCR assays. Three software programs were used to select the most suitable reference miRNAs from among the 4 candidate reference miRNAs. Expression of the 4 target miRNAs was then calculated relative to expression of the reference genes in plasma and EVs, and relative expression was compared between dogs with glioma and control dogs with other brain diseases. RESULTS The most suitable reference miRNAs were miR-16 for plasma and let-7a for EVs. Relative expression of miR-15b in plasma and in EVs was significantly higher in dogs with glioma than in control dogs. Relative expression of miR-342-3p in EVs was significantly higher in dogs with glioma than in control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that miR-15b and miR-342-3p have potential as noninvasive biomarkers for differentiating glioma from other intracranial diseases in dogs. However, more extensive analysis of expression in specific glioma subtypes and grades, compared with expression in more defined control populations, will be necessary to assess their clinical relevance.

Endoplasmic reticulum (ER) stress and oxidative stress lead to protein misfolding, and the resulting accumulation of protein aggregates is often associated with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and prion disease. Small molecules preventing these pathogenic processes may be effective interventions for such neurodegenerative disorders. In this paper, we identify several novel oxindole compounds that can prevent ER stress- and oxidative stress-induced cell death. Among them, derivatives of the lead compound GIF-0726-r in which a hydrogen atom at the oxindole ring 5 position is substituted with a methyl (GIF-0852-r), bromine (GIF-0854-r), or nitro (GIF-0856-r) group potently suppressed global ER stress. Furthermore, GIF-0854-r and -0856-r prevented protein aggregate accumulation

Degenerative myelopathy (DM) is an adult-onset, progressive neurological disease affecting several breeds of dog. Homozygosity or compound heterozygosity for the canine superoxide dismutase 1 (SOD1) gene mutations, possibly modulated by the modifier SP110 locus, are associated with a high risk for DM. Although the pathophysiological mechanisms are largely unknown, a role for mutant SOD1 in causing neuronal degeneration has been postulated. Three Hovawart dogs, 9e12 years of age, developed slowly progressive incoordination and weakness of the pelvic limbs leading to non-ambulatory flaccid paraparesis and muscle atrophy. Neuropathological lesions comprised axonal degeneration and loss of ascending and descending spinal pathways, which were most severe in the mid- to caudal thoracic segments. Accumulation of mutant SOD1 protein in neurons and reactive astrocytes was demonstrated by immunolabelling with the 16G9 antibody against the mutant SOD1 protein (p.E40K amino acid substitution). All three dogs were homozygous for the c.118A allele, but none had the SP110 ‘risk’ haplotype, suggesting a weak association of SP110 with the onset of DM in this breed. Our data suggest that the Hovawart breed is predisposed to the SOD1:c.118G>A mutation, which is associated with the development of DM. Prevention of DM could be achieved with the help of strategies based on epidemiological and genetic testing.

A 1-year- and 11-month-old spayed female toy poodle had showed progressive ataxia and paresis in the hindlimbs since 11 months old. Magnetic resonance imaging revealed high signal intensity on T2-weighted and fluid-attenuated inversion recovery images at the thoracic and lumbar spinal cord. The dog’s neurological condition slowly deteriorated and flaccid tetraparesis was exhibited. At 4 years and 11 months old, the dog died of respiratory failure. On postmortem examination, eosinophilic corkscrew bundles (Rosenthal fibers) were observed mainly in the thoracic and lumbar spinal cord. Histological features were comparable to previously reported cases with Alexander disease. This is a first case report to describe the clinical course and long-term prognosis of a dog with Alexander disease.

A 9-year-old neutered male Wire Fox Terrier presented with an 1-month history of hindlimb paresis. Magnetic resonance imaging revealed a contrast-enhanced mass at the level of the L2 vertebral canal. The dog became paraplegic with no deep perception of the hindlimbs, and the mass was surgically removed. The histopathological diagnosis was of a malignant peripheral nerve sheath tumor (MPNST). The dog suffered a relapse of right hindlimb ataxia at 225 days after the surgery. The dog died 434 days after the surgery. Necropsy found a large mass in the abdominal cavity invading from the L2-nerve. This is the first report of MPNST invading the abdominal cavity through the nerve root.

Thoracolumbar intervertebral disk herniation (TL-IVDH) with caudal articular process anomalies has been reported in Pugs. It currently remains unclear whether congenital caudal articular process aplasia/hypoplasia predisposes to the development of TL-IVDH. However, there are difficulties in proving the causal relationship between caudal articular process anomalies and TL-IVDH. The aim of this study was to describe the prevalence of TL-IVDH at the vertebral space containing anomalous and normal caudal articular processes in Pugs. Fifty-seven pugs were eligible to be included in this study. Caudal articular process aplasia/hypoplasia affected 52/57 (91.2%) dogs. The caudal articular process anomalies were most frequently located between T10 and T13. Colocalization of caudal articular process aplasia/hypoplasia and TL-IVDH was detected in 11 dogs (19.3%). The prevalence of TL-IVDH at vertebral spaces containing abnormal caudal articular processes was 12.3%, whereas the prevalence of TL-IVDH at vertebral spaces containing normal articular processes was 2.4%. With the increase in the number of vertebrae with caudal articular process anomalies, the prevalence of TL-IVDH also increased. The results of this study suggested the prevalence of caudal articular process anomalies was high in Pugs. The caudal articular process anomalies could be associated with TL-IVDH. A large cohort is needed to prove the causal relationship between caudal articular process anomalies and TL-IVDH.

Simple Summary Canine degenerative myelopathy (DM) is a chronic, progressive, and fatal neurodegenerative disease. Although degenerative changes in dogs with DM are observed not only in the spinal cord white matter but also the dorsal root ganglion (DRG) neurons, these changes are undetectable on conventional magnetic resonance imaging (MRI). Therefore, we investigated the ability of water-excitation MRI to visualize the DRG in dogs, and whether volumetry of DRG has a premortem diagnostic value for DM. Using water-excitation MRI, DRG could be depicted in all dogs. To normalize the volumes of DRG, body surface area was the most suitable denominator. The normalized DRG volume in dogs with DM was significantly lower than those in control dogs and dogs with intervertebral disc herniation. The results of this study revealed that widespread atrophy of DRG was likely to occur in DM. Moreover, volume reductions of DRG were observed in dogs with DM in both the early disease stage and late disease stage. Our research suggests that the DRG volume obtained by the water-excitation technique could be used as a clinical biomarker for DM. Abstract Canine degenerative myelopathy (DM) is a progressive and fatal neurodegenerative disease. However, a definitive diagnosis of DM can only be achieved by postmortem histopathological examination of the spinal cord. The purpose of this study was to investigate whether the volumetry of DRG using the ability of water-excitation magnetic resonance imaging (MRI) to visualize the DRG in dogs has premortem diagnostic value for DM. Eight dogs with DM, twenty-four dogs with intervertebral disc herniation (IVDH), and eight control dogs were scanned using a 3.0-tesla MRI system, and water-excitation images were obtained to visualize and measure the volume of DRG, normalized by body surface area. The normalized mean DRG volume between each spinal cord segment and mean volume of all DRG between T8 and L2 in the DM group was significantly lower than that in the control and the IVDH groups (P = 0.011, P = 0.002, respectively). There were no correlations within the normalized mean DRG volume between DM stage 1 and stage 4 (rs = 0.312, P = 0.128, respectively). In conclusion, DRG volumetry by the water-excitation MRI provides a non-invasive and quantitative assessment of neurodegeneration in DRG and may have diagnostic potential for DM.

Canine degenerative myelopathy (DM) is a fatal progressive neurodegenerative disease. Mutations in the superoxide dismutase 1 (SOD1) gene have been shown to be the major risk factor for DM, and it is hypothesized that neural degeneration is caused by a “gain of toxic function” of mutant SOD1. In this study, the spinal cord microRNA (miRNA) profiles of DM-affected dogs were investigated to elucidate the pathomechanisms of DM. Quantification of 277 miRNAs identified three up-regulated miRNAs and 18 down-regulated miRNAs in the spinal cords of DM-affected dogs. Based on gene ontology analysis, the target cluster of up-regulated miRNAs was associated with protein expression or modification and cellular response, and that of down-regulated miRNAs was associated with tissue development. In these clusters, we focused on the mechanism of protein ubiquitination. Polyubiquitination assay demonstrated that canine SOD1 proteins were polyubiquitinated and degraded by proteasomes. Immunohistochemistry of the spinal cords of DM-affected dogs showed that mutant SOD1 aggregations were not ubiquitin immunopositive. Using cultured cells, co-transfection of canine SOD1 and up-regulated miRNA in DM-affected dogs demonstrated that miR-23a, miR-142 and miR-221 significantly increased the proportion of cells with mutant SOD1 aggregation. These results suggested that up-regulated miRNAs in the spinal cords of DM-affected dogs may inhibit ubiquitination of misfolded SOD1 protein and induce mutant SOD1 aggregations, leading to further progression of degenerative processes in the DM pathology.

Canine degenerative myelopathy (DM) is a progressive neurodegenerative disorder, which is commonly associated with c.118G A (p. E40K) missense mutation in the superoxide dismutase 1 (SOD1) gene. Mutant SOD1 protein (SOD1

Canine degenerative myelopathy (DM) is an adult-onset fatal disease characterized by progressive degeneration of the spinal cord. Affected dogs have homozygous mutations in superoxide dismutase 1, and thus DM is a potential spontaneous animal model of human familial amyotrophic lateral sclerosis (ALS). Neuroinflammation is the pathological hallmark of ALS, whereby proinflammatory cytokines and chemokines are overproduced by activated glial cells such as astrocytes and microglia. However, the detailed pathogenesis of spinal cord degeneration in DM remains unknown. To further characterize the pathological mechanism of DM, we analyzed the caudal cervical cords of ten Pembroke Welsh Corgis pathologically diagnosed with DM by quantitative real-time reverse transcription polymerase chain reaction, immunohistochemistry (IHC), and double immunofluorescence. Compared to control spinal cord tissues, we found significantly enhanced transcriptions of interleukin-1β, tumor necrosis factor-α, CC motif chemokine ligand (CCL) 2 and vascular cell adhesion molecule -1 mRNA in the spinal cords of DM dogs. Moreover, IHC for the class II major histocompatibility complex molecules HLA-DR and CCL2 indicated that the immunopositive areas of activated macrophages/microglia and CCL2 protein were significantly increased in DM, and CCL2 protein was mainly overproduced by astrocytes. Our results suggest a proinflammatory state of the microenvironment in the DM spinal cord in which activated microglia and astrocytes play important roles by secreting a set of cytokines, chemokines, and expressing adhesion molecules.

A 4-year-old male Toy Poodle was presented with a history of status epilepticus. On presentation, neurological examination revealed a delay in postural reactions in the right pelvic limb. Magnetic resonance imaging showed a fluid-containing cystic lesion that compressed the mesencephalon, hippocampus, and amygdala. The cyst was surgically removed via left rostrotentorial craniotomy. The final diagnosis was an intracranial ectopic choroid plexus cyst. The patient has remained free of seizures for 18 months after surgery. This is the first case report of an intracranial ectopic choroid plexus cyst that was surgically removed in a dog.

Amyloidogenic proteins form aggregates in cells, thereby leading to neurodegenerative disorders, including Alzheimer's and prion's disease, amyotrophic lateral sclerosis (ALS) in humans, and degenerative myelopathy (DM) and cognitive dysfunction in dogs. Hence, many small-molecule compounds have been screened to examine their inhibitory effects on amyloidogenic protein aggregation. However, no effective drug suitable for transition to clinical use has been found. Here we examined several novel oxindole compounds (GIF compounds) for their inhibitory effects on aggregate formation of the canine mutant superoxide dismutase 1 (cSOD1 E40K), a causative mutation resulting in DM, using Thioflavin-T fluorescence. Most GIF compounds inhibited the aggregation of cSOD1 E40K. Among the compounds, GIF-0854-r and GIF-0890-r were most effective. Their inhibitory effects were also observed in cSOD1 E40K-transfected cells. Additionally, GIF-0890-r effectively inhibited the aggregate formation of human SOD1 G93A, a causative mutation of ALS. GIF-0827-r and GIF-0856-r also effectively inhibited aggregate formation of human prion protein (hPrP). Subsequently, the correlation between their inhibitory effects on cSOD1 and hPrP aggregation was shown, indicating GIF compounds inhibited the aggregate formation of multiple amyloidogenic proteins. Conclusively, the novel oxindole compounds (GIF-0827-r, GIF-0854-r, GIF-0856-r, and GIF-0890-r) are proposed as useful therapeutic candidates for amyloidogenic neurodegenerative disorders.

Objective To evaluate the accuracy and safety of a novel patient-specific drill guide template for stabilizing the thoracolumbar vertebrae of dogs. Study design Cadaveric experimental study and prospective case series. Sample population Cadaveric canine thoracolumbar vertebral specimens (n = 3) and clinical cases of thoracolumbar spinal instability (n = 4). Methods Computed tomography data of the thoracolumbar spines were obtained before surgery, and images were imported into imaging software. Optimum screw trajectories were selected for each vertebra, and drill guide templates were designed and fabricated with a 3-dimensional printing system. Drill guide templates were applied to cadaveric spine and clinical cases. Computed tomography imaging was performed after surgery, and planned and postoperative trajectories were compared to estimate the accuracy and safety of the drill guide templates. Results Twenty-two drill holes were made in cadaveric spinal specimens. All drill holes were completely located in the bone. The overall mean screw deviation was 0.88 ± 0.36 mm. In clinical cases, 29 screws were placed in thoracolumbar vertebrae. Most (89.6%) of these screws were placed without evidence of vertebral canal invasion. One (3.5%) screw perforated the bone structure. The overall mean screw deviation was 1.16 ± 0.56 mm. Conclusion Drill guide templates were useful for accurate intraoperative screw navigation in thoracolumbar fixation in small dogs. Clinical significance The use of drill guide templates can be considered as an aid to safety and accuracy of screw placement in canine thoracolumbar instabilities.

An 8-year-old castrated male cat presented with acute ataxia and paresis in all four limbs. The cat also exhibited signs of autonomic nervous system impairment. Magnetic resonance imaging revealed swelling of the brachial plexuses bilaterally. Despite treatment, the cat died after 10 days of treatment. A postmortem examination revealed swollen radial nerves and cervical nerve roots in which infiltration of inflammatory cells was histologically confirmed. Additionally, lymphocytic infiltration was found around the blood vessels of the sciatic nerve bundle and the vagus nerve. Histological features were comparable to previously reported brachial plexus hypertrophic neuritis in a cat. Our case was unique in that the autonomic nerves were also involved in addition to the somatic nerves in all four limbs.

A 4-year-old, male Bernese mountain dog was evaluated for a 1-year history of right hemiparesis. Computed tomography revealed a large hypoattenuating mass severely deforming the C5 vertebral arch, invading the C6 spinal canal, and causing spinal cord compression. The signal characteristics of magnetic resonance imaging indicated a lesion composed of adipose tissue. The mass was removed via right hemilaminectomy, and histopathological examination confirmed it was an infiltrative lipoma. The compressive lesion remained unresolved, so the dog underwent a second operation, after which he regained some ambulatory function. Although postoperative adjunctive radiation therapy was performed, the dog died 201 days after the first operation.

OBJECTIVE To compare ultracentrifugation, precipitation, and membrane affinity chromatography methods for isolation of extracellular vesicles (EVs) from canine plasma samples and to identify suitable reference genes for incorporation into a quantitative reverse transcription PCR assay of microRNA expression in plasma EVs of healthy dogs. ANIMALS 6 healthy Beagles. PROCEDURES Plasma samples were obtained from each dog, and EVs were isolated from 0.3 mL of these samples via ultracentrifugation, precipitation, and membrane-affinity chromatographic methods. Nanoparticle tracking analysis was performed to determine the concentration and size distribution of EVs isolated by the ultracentrifugation method. Expression levels (cycle threshold values) of 4 microRNAs (let-7a, miR-16, miR-26a, and miR-103) were then compared by means of quantitative reverse transcription PCR assay. Three statistical programs were used to identify the microRNAs most suitable for use as reference genes. RESULTS Results indicated that ultracentrifugation was the most stable of all 3 methods for isolating microRNAs from 0.3 mL of plasma. Nanoparticle tracking revealed that EV samples obtained by the ultracentrifugation method contained a mean ± SD of approximately 1.59 × 1010 vesicles/mL ± 4.2 × 108 vesicles/mL. Of the 4 microRNAs in plasma EVs isolated by ultracentrifugation, miR-103 was the most stable. CONCLUSIONS AND CLINICAL RELEVANCE The ultracentrifugation method has potential as a stable method for isolating EVs from canine plasma samples with a high recovery rate, and miR-103 may provide the most stable reference gene for normalizing microRNA expression data pertaining to plasma EVs isolated by ultracentrifugation.

Canine glioma is a common brain tumor with poor prognosis despite surgery and/or radiation therapy. Therefore, newer and more effective treatment modalities are needed. Neuregulin 3 (NRG3) has known to be a ligand of ERBB4. This study aimed to investigate the usefulness of the NRG3/ERBB4 signaling cascade as a novel therapeutic target in canine glioma. We found out that microRNA (miR)-190a was downregulated in canine brain tumor tissues, including glioma and meningioma. miR-190a directly targeted NRG3 and inhibited the growth of canine glioma cells. The level of p-Akt, which is a downstream target of ERBB4 signaling, was decreased by transfection with miR-190a. NRG3 silencing also suppressed cell growth and decreased the levels of p-Akt and p-ERK1/2, and NRG3 overexpression exhibited opposed effects in canine glioma J3T-1 cells. The mRNA level of erbb4 was significantly upregulated in glioma tissues compared with that in normal brain tissues and meningioma tissues. Furthermore, compared with gefitinib and lapatinib, afatinib exerted a greater inhibitory effect on the growth of canine glioma cells. In conclusion, NRG3/ERBB4 signaling is negatively regulated by miR-190a and contributes to the growth of canine glioma cells, indicating that it may be a promising therapeutic target in canine glioma.

Canine degenerative myelopathy (DM) is an adult-onset, progressive neurodegenerative disease that occurs in multiple dog breeds. A DM-associated mutation of the canine superoxide dismutase 1 (SOD1) gene, designated as c.118G>A (p.E40K), has been implicated as one of pathogenetic determinants of the disease in many breeds, but it remains to be determined whether the c.118G>A mutation is responsible for development or progression of DM in Collies. Previously, a Rough Collie was diagnosed clinically and histopathologically as having DM in Japan, suggesting the possibility that the Collie breed may be predisposed to DM due to the high frequency of c.118G>A in Japan. In this study, accumulation and aggregate formation of SOD1 protein were retrospectively demonstrated in the spinal cord of the DM-affected dog by immunohistochemical analysis. Furthermore, a molecular epidemiological survey revealed a high carrier rate (27.6%) and mutant allele frequency (0.138) of c.118G>A in a population of Collies in Japan, suggesting that the Collie breed may be predisposed to DM associated with c.118G>A, and the prevention of DM in Collies in Japan should be addressed through epidemiological and genetic testing strategies.

Canine degenerative myelopathy (DM) is a progressive and fatal neurodegenerative disorder that has been linked to mutations in the superoxide dismutase 1 (SOD1) gene. The accumulation of misfolded protein aggregates in spinal neurons and astrocytes is implicated as an important pathological process in DM; however, the mechanism of protein aggregate formation is largely unknown. In human neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), cell-to-cell propagation of disease-relevant proteins has been demonstrated. Therefore, in this study, propagation of aggregation-forming property of mutant SOD1 protein in DM in vitro was investigated. This study demonstrated that aggregates composed of canine wild type SOD1 protein were increased by co-transfection with canine mutant SOD1 (E40K SOD1), indicating intracellular propagation of SOD1 aggregates. Further, aggregated recombinant SOD1 proteins were released from the cells, taken up by other cells, and induced further aggregate formation of normally folded SOD1 proteins. These results suggest intercellular propagation of SOD1 aggregates. The hypothesis of cell-to-cell propagation of SOD1 aggregates proposed in this study may underly the progressive nature of DM pathology.

Atlantoaxial instability (AAI)/subluxation commonly occurs in small breed dogs. Ventral stabilization techniques using screws and/or pins and a plate or, more commonly, polymethylmethacrylate are considered to provide the most favorable outcome. However, the implantation of screws of sufficient sizes for long-term stability becomes challenging in toy breed dogs (e.g.

BACKGROUND In canine epitheliotropic cutaneous T-cell lymphoma (ECTCL), neoplastic cells cause skin lesions and potentially metastasize to lymph nodes, blood and other organs. Murine models are potentially valuable for elucidating the molecular mechanisms responsible for regulation of ECTCL cell migration. HYPOTHESIS/OBJECTIVES To describe a phenotype of mice xenografted with canine ECTCL cells (EO-1 cells). ANIMALS Four NOD.CB17-Prkdcscid /J (NOD SCID) mice were used. METHODS AND MATERIALS EO-1 cells were subcutaneously xenografted into NOD SCID mice. After four weeks, the development of tumour lesions in skin and other organs was investigated. RESULTS Mice developed skin lesions with metastasis to the lymph nodes, spleen, lung, blood and liver. CONCLUSIONS AND CLINICAL IMPORTANCE Mice xenografted with EO-1 cells may be useful for studying the pathogenesis of canine ECTCL.