Correlation of mitochondrial protein expression in complexes I to V with natural and induced forms of canine idiopathic dilated cardiomyopathy

OBJECTIVE: To identify qualitative and quantitative differences in cardiac mitochondrial protein expression in complexes I to V between healthy dogs and dogs with natural or induced dilated cardiomyopathy (DCM). SAMPLE POPULATION: Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with DCM induced by rapid right ventricular pacing. PROCEDURES: Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by 2-fold or greater between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. RESULTS: A total of 22 altered mitochondrial proteins were identified in complexes I to V. Ten and 12 were found in complex I and complexes II to V, respectively. Five were mitochondrial encoded, and 17 were nuclear encoded. Most altered mitochondrial proteins in tissue specimens from dogs with naturally occurring DCM were associated with complexes I and V, whereas in tissue specimens from dogs subjected to rapid ventricular pacing, complexes I and IV were more affected. In the experimentally induced form of DCM, only nuclear-encoded subunits were changed in complex I. In both disease groups, the 22-kd subunit was downregulated. CONCLUSIONS AND CLINICAL RELEVANCE: Natural and induced forms of DCM resulted in altered mitochondrial protein expression in complexes I to V. However, subcellular differences between the experimental and naturally occurring forms of DCM may exist.     

Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis

OBJECTIVE: To perform polymerase chain reaction (PCR) analysis on paraffin-embedded myocardium from dogs with dilated cardiomyopathy (DCM) and dogs with myocarditis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus. SAMPLE POPULATION: Myocardial specimens from 18 dogs with an antemortem diagnosis of DCM and 9 dogs with a histopathologic diagnosis of myocarditis were evaluated. PROCEDURE: Paraffin-embedded myocardial specimens were screened for viral genome by PCR analysis. Positive-control specimens were developed from cell cultures as well as paraffin-embedded tissue specimens from dogs with clinical and histopathologic diagnoses of viral infection with canine parvovirus, adenovirus types 1 and 2, and herpesvirus. The histologic characteristics of all myocardial specimens were classified regarding extent, location, and type of inflammation and fibrosis. RESULTS: Canine adenovirus type 1 was amplified from 1 specimen from a dog with DCM. Canine parvovirus, adenovirus type 2, and herpesvirus were not amplified from any myocardial specimens. Histologic analysis of specimens from dogs with DCM revealed variable amounts of fibrosis; myocardial inflammation was observed in 1 affected dog. Histopathologic analysis of specimens from dogs with myocarditis disclosed variable degrees of inflammation and fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Viral agents canine parvovirus, adenovirus types 1 and 2, and herpesvirus are not commonly associated with DCM or active myocarditis in dogs. Additional studies evaluating for nucleic acid from viruses that less commonly affect dogs or different types of infectious agents may be warranted to gain insight into the cause of DCM and myocarditis in dogs.     

Concentrations of cartilage oligomeric matrix protein in dogs with naturally developing and experimentally induced arthropathy

OBJECTIVE: To assay concentrations of cartilage oligomeric matrix protein (COMP) in canine sera and synovial fluid (SF), to compare COMP concentrations in clinically normal dogs and dogs with joint disease, and to analyze changes in COMP concentrations in dogs with experimentally induced acute synovitis. ANIMALS: 69 control dogs without joint disease, 23 dogs with naturally occurring aseptic arthropathy, and 6 dogs with experimentally induced synovitis. PROCEDURE: Serum (n = 69) and SF (36) were obtained from control dogs. Samples of serum (n = 23) and SF (13) were obtained from dogs with naturally occurring aseptic arthropathy with or without radiographic features of osteoarthritis (OA). Serum and SF were obtained before and 1, 2, 3, and 7 days after induction of synovitis. The COMP concentrations were determined by use of an inhibition ELISA that had canine cartilage COMP and monoclonal antibody against human COMP. RESULTS: Concentrations of COMP in serum and SF of control dogs were 31.3+/-15.3 and 298.7+/-124.7 microg/ml, respectively. In naturally occurring OA, COMP concentrations in serum (44.9+/-177 microg/ml) and SF (401.7+/-74.3 microg/ml) were significantly higher than corresponding concentrations in control dogs. The COMP concentration in SF peaked 24 and 48 hours after induction of synovitis, whereas concentration in serum peaked on day 3. CONCLUSIONS AND CLINICAL RELEVANCE: These results supported the hypothesis that COMP concentration in serum and SF of dogs may be altered after cartilage degradation or synovitis. Measurement of COMP concentrations can be useful when differentiating arthropathies in dogs.     

Results of hyperamplification of centrosomes in naturally developing tumors of dogs.

OBJECTIVE: To evaluate results of centrosome hyperamplification in naturally developing tumors of dogs. SAMPLE POPULATION: Tumor specimens from 9 dogs with tumors (rhabdomyosarcoma, osteosarcoma, chondrosarcoma, myxosarcoma, and mammary gland tumor) and 2 canine osteosarcoma cell lines. PROCEDURE: 3 antibodies for centrosome proteins (ie, anti-gamma-tubulin, anti-BRCA1, and anti-pericentrin) were used for immunohistochemical analysis. Double immunostaining for centrosomes was used to confirm the specificity of these antibodies for centrosomes. Mutational analysis of the canine p53 gene was carried out by polymerase chain reaction-single-strand conformation polymorphism analysis, and expression of canine MDM2 protein was evaluated by use of immunohistochemical analysis, using anti-MDM2 antibody. RESULTS: Immunohistochemical analysis of dog osteosarcoma cell lines with apparent aneuploidy revealed frequent hyperamplification of centrosomes in the osteosarcoma cell lines. Similar hyperamplified centrosomes were detected in the tumor tissues from all of the 9 tumors. The frequency of cells with hyperamplified centrosomes (3 to 20/cell) in each tumor tissue ranged from 9.50 to 48.1%, whereas centrosome hyperamplification was not observed in normal lymph nodes from these dogs. In 8 of the 9 tumors, mutation of p53 gene or overexpression of MDM2, or both, was detected. CONCLUSIONS AND CLINICAL RELEVANCE: Various types of naturally developing tumors in dogs often have hyperamplification of centrosomes associated with chromosome instability. Hyperamplification of centrosomes is a novel tumor marker for use in cytologic and histologic examinations of clinical specimens obtained from dogs.     

Telomere length and telomerase activity in canine mammary gland tumors

OBJECTIVE: To measure telomere length and telomerase activity in naturally occurring canine mammary gland tumors. SAMPLE POPULATION: 27 mammary gland tumor specimens obtained during resection or necropsy and 12 mammary gland tissue specimens obtained from healthy (control) dogs. PROCEDURE: Telomere length in tissue specimens was measured by use of restriction endonuclease digestion and Southern blot analysis. Telomerase activity was measured by use of a telomeric repeat amplification protocol assay. RESULTS: Telomere length in mammary gland tumors ranged from 11.0 to 21.6 kilobase pairs (kbp; mean +/- SEM, 14.5+/-0.5 kbp) but did not differ among tumor types. Telomeres in mammary gland tumors were slightly shorter than in normal tissue specimens, but telomere length could not be directly compared between groups, because mean age of dogs was significantly different between groups. Age was negatively correlated with telomere length in control dogs but was not significantly correlated with length in affected dogs. Telomerase activity was detected in 26 of 27 mammary gland tumors and in 4 of 12 normal tissue specimens. However, telomerase activity and telomere length were not correlated in tumor specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Telomere length is maintained in canine mammary gland tumors regardless of the age of the affected dog. Measurement of telomere length may be a useful tool for monitoring the in vivo effects of telomerase inhibitors in dogs with tumors.     

Serum concentration of some acute phase proteins in naturally occurring canine babesiosis: a preliminary study

BACKGROUND: Serum concentrations of acute phase proteins can provide valuable diagnostic information in the detection, prognosis, or monitoring of disease. Information available on the acute phase response in naturally occurring canine babesiosis is limited. OBJECTIVE: The purpose of this investigation was to retrospectively evaluate serum concentrations of haptoglobin, C-reactive protein, and ceruloplasmin in dogs naturally infected with Babesia canis. METHODS: Haptoglobin, C-reactive protein, and ceruloplasmin concentrations were measured in serum samples from dogs with uncomplicated (n = 6) and complicated (n = 1) babesiosis and compared with 6 healthy dogs. RESULTS: Serum C-reactive protein and ceruloplasmin concentrations were significantly higher in dogs with babesiosis; however, serum haptoglobin concentration was significantly lower compared with control dogs (P <.01). CONCLUSIONS: Results of this study suggest that acute phase protein concentrations could be beneficial in the diagnosis and determination of the severity of babesiosis in dogs.     

The immunohistochemical evaluation of selected markers in the left atrium of dogs with end-stage dilated cardiomyopathy and myxomatous mitral valve disease – a preliminary study

Background

Dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD) are the most common diseases noted in dogs. Although their pathogenesis varies, both include a significant enlargement of the left atrium.The study was carried out on left atrial specimens obtained from 56 dogs, including those from 34 dogs with clinically diagnosed MMVD, 15 dogs with DCM and 7 dogs without heart disease (control group). Dogs in the MMVD and the DCM groups presented with left atrial enlargement and stage D heart failure. The specimens underwent immunohistochemical examination using desmin, vimentin, periostin and caspase-3 antibodies.

Results

There were alterations in the expression of the studied proteins in the study groups compared to the control group. The changes included: irregularity of desmin cross-striation and desmosomes, a higher amount of vimentin-positive cells, a change in the periostin expression pattern from cytoplasmic to extracellular, and a lower expression of caspase-3. The alterations were more pronounced in the DCM group than in the MMVD group.

Conclusions

During heart failure, the pattern of desmin, vimentin, periostin and caspase-3 expression alters in the left atrium, regardless of the cause. The changes are more pronounced in dogs with DCM than in dogs with MMVD and similar left atrial enlargement, suggesting that volume overload may not be the only cause of myocardial changes in DCM.

     

Quantification of mucin gene expression in tracheobronchial epithelium of healthy dogs and dogs with chronic bronchitis

OBJECTIVE: To develop a real-time PCR assay for the quantification of mucin gene expression in tracheobronchial brushing specimens from dogs and compare mucin gene expression in specimens from dogs with naturally occurring chronic bronchitis with that in specimens from healthy dogs. ANIMALS: 7 healthy dogs and 5 dogs with chronic bronchitis. PROCEDURES: Primers that were designed to span the predicted intron-exon boundaries of a canine MUC5AC-like gene were used to develop a real-time PCR assay for quantification of expression of that gene. Total mRNA was isolated from tracheobronchial brushing specimens obtained from dogs with and without bronchitis during anesthesia; MUC5AC-like gene expression in those samples was quantified by use of the real-time PCR assay. RESULTS: The PCR assay was sensitive and specific for the target sequence, the predicted amino acid sequence of which had greatest homology with human, porcine, and rat MUC5AC. The assay was able to quantify the target over a wide dynamic range. Dogs with chronic bronchitis had a 3.0-fold increase in the quantity of MUC5AC-like mRNA, compared with healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The ability to measure mucin gene expression from tracheobronchial brushing specimens collected from client-owned dogs during routine bronchoscopy should prove to be a useful tool for the study of bronchitis in dogs and expand the usefulness of airway inflammation in dogs as a model for bronchitis in humans.     

Electrophoretic determination of albumin and gamma globulin concentrations in the cerebrospinal fluid of dogs with encephalomyelitis attributable to canine distemper virus infection: 13 cases (1980-1987)

Thirteen dogs with encephalomyelitis attributable to canine distemper virus infection were classified into 3 groups on the basis of histopathologic evidence of virus-induced lesions in CNS tissue. Analysis of data indicated a similarity within groups when arranged by age, clinical neurologic signs, and alterations in the CSF electrophoretic protein values. Comparison with results in dogs with experimentally induced canine distemper encephalomyelitis suggested that when grouped by age, CSF electrophoretic values are helpful in predicting the CNS histopathologic changes in dogs with naturally acquired canine distemper encephalomyelitis.     

Plasma antioxidant capacity in dogs with naturally occurring heart diseases

The aim of the study was to compare the plasma levels of antioxidants by measuring total antioxidant activity (TAS) and ferric reducing ability of the plasma (FRAP) in healthy dogs and in those that are suffering from dilated cardiomyopathy (DCM) or from mitral endocardiosis (ME). Dogs with echocardiographically diagnosed ME (10 dogs) as well as DCM (23 dogs) were sampled. Of dogs with DCM, eight having DCM with sinus rhythm (SR) were included in the DCM-SR group and 15 having DCM with atrial fibrillation (AF) in the DCM-AF group. Total antioxidant levels measured by TAS assay differed neither significantly between the cardiac patients and the control group nor between the heart disease groups. Ferric reducing ability of the plasma in animals with cardiac disease was significantly higher than in the control animals, and the difference was also significant in between the two DCM groups. However, the differences between the antioxidant levels of the DCM and ME groups did not reach significance in none of the antioxidant (TAS and FRAP) tests. Summarizing the results of this study it can be concluded that there is an increased antioxidant reactivity detected by the FRAP, but not by the TAS assay in the blood of dogs with naturally occurring cardiac disorders. The magnitude of this increase seems to be more affected rather by the severity of the cardiac insufficiency and/or by the heart rate or rhythm disorder than by the underlying heart disease itself.     

Evaluation of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy

OBJECTIVE: To evaluate the role of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy (DCM). ANIMALS: 6 dogs with DCM, including 2 Doberman Pinschers, 2 Newfoundlands, and 2 Great Danes. PROCEDURE: All dogs had clinical signs of congestive heart failure, and a diagnosis of DCM was made on the basis of echocardiographic findings. Blood samples were collected from each dog, and genomic DNA was isolated by a salt extraction method. Specific oligonucleotides were designed to amplify the promoter, exon 1, the 5'-part of exon 2 including the complete coding region, and part of intron 1 of the canine phospholamban gene via polymerase chain reaction procedures. These regions were screened for mutations in DNA obtained from the 6 dogs with DCM. RESULTS: No mutations were identified in the promoter, 5' untranslated region, part of intron 1, part of the 3' untranslated region, and the complete coding region of the phospholamban gene in dogs with DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that mutations in the phospholamban gene are not a frequent cause of DCM in Doberman Pinschers, Newfoundlands, and Great Danes.     

Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy

OBJECTIVE: To sequence the exonic and splice site regions of 5 cardiac genes associated with the human form of familial dilated cardiomyopathy (DCM) in Doberman Pinschers with DCM and to identify a causative mutation. ANIMALS: 5 unrelated Doberman Pinschers with DCM and 2 unaffected Labrador Retrievers (control dogs). PROCEDURES: Exonic and splice site regions of the 5 genes encoding the cardiac proteins troponin C, lamin A/C, cysteine- and glycine-rich protein 3, cardiac troponin T, and the beta-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected dogs and the published canine sequences and 2 control dogs. Base pair changes were considered to be causative for DCM if they were present in an affected dog but not in the control dogs or published sequences and if they involved a conserved amino acid and changed that amino acid to a different polarity, acid-base status, or structure. RESULTS: A causative mutation for DCM in Doberman Pinschers was not identified, although single nucleotide polymorphisms were detected in some dogs in the cysteine- and glycine-rich protein 3, beta-myosin heavy chain, and troponin T genes. CONCLUSIONS AND CLINICAL RELEVANCE: Mutations in 5 of the cardiac genes associated with the development of DCM in humans did not appear to be causative for DCM in Doberman Pinschers. Continued evaluation of additional candidate genes or a focused approach with an association analysis is warranted to elucidate the molecular cause of this important cardiac disease in Doberman Pinschers.     

Isolation, characterization, and expression of stromelysin-1 in primary tumors of dogs

OBJECTIVE: To isolate and characterize the cDNA sequence of canine stromelysin-1 (matrix metalloproteinase [MMPI-3), screen various naturally developing primary tumors of dogs, and assess the effect of stromelysin-1 on survival of dogs with cancer. SAMPLE POPULATION: 3 canine cell lines and biopsy specimens of primary tumors collected from 54 dogs. PROCEDURE: 3 canine cell lines and biopsy specimens of primary tumors collected from 54 dogs at the University of Illinois Veterinary Teaching Hospital were used in the study. Primer sets based on human stromelysin-1 and consensus sequences were designed for expression, screening, and isolation. Two additional primer sets were designed for screening. Samples were assayed at least in duplicate. Data were analyzed for differences in expression of stromelysin-1 on the basis of sex, age, metastasis, malignant versus nonmalignant tissue origin, and duration of patient survival. RESULTS: A 1,479-bp cDNA nucleotide sequence was amplified from established canine cell lines. The open reading frame encoded a protein consisting of 478 amino acids. This sequence was 70% to 88% homologous with stromelysin-1 of other species at the amino acid level. Fifty-four samples were screened for stromelysin-1. Of these, 34 (63%) had positive results and 20 (37%) had negative results for expression. Stromelysin-1 and metastasis were associated with a poor prognosis for survival. CONCLUSIONS AND CLINICAL RELEVANCE: Stromelysin-1 is a potential activator of other members of the MMP family. Additional studies are needed to investigate the relationship between stromelysin-1 production and aggressive biological behavior of tumors in dogs.     

Assessment of regional systolic and diastolic myocardial function using tissue Doppler and strain imaging in dogs with dilated cardiomyopathy

BACKGROUND: Tissue Doppler Imaging (TDI) or strain (St) imaging could provide sensitive indices for early detection and treatment follow-up of canine dilated cardiomyopathy (DCM). Analysis of TDI and St features in dogs with overt DCM is a prerequisite before using these new criteria in prospective screenings of predisposed families or in clinical trials. HYPOTHESIS: Radial and longitudinal right and left myocardial motion, assessed by TDI and St variables, is altered in dogs with DCM. ANIMALS: Case records for 26 dogs; 14 with DCM and 12 healthy controls of comparable age and weight were reviewed. METHODS: A retrospective analysis was conducted of conventional echocardiography, 2-dimensional color TDI, and St imaging data. RESULTS: The DCM group was characterized by decreases in radial and longitudinal systolic velocity gradients of the left ventricular free wall (LVFW), radial and longitudinal absolute values of peak systolic St of the LVFW, and longitudinal systolic right ventricular (RV) velocities (all P < .001 versus control) associated with longitudinal postsystolic contraction waves in 7/14 dogs. Early diastolic LVFW velocities also were decreased for longitudinal (P < .01) and radial (P < .05) motions. All radial LVFW, longitudinal basal LVFW, and RV systolic velocities were negatively correlated with heart rate (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: LV contractility along both the short and long axes is impaired in dogs with spontaneous DCM, as is systolic RV and diastolic LVFW function. These myocardial alterations are associated with an inverse force-frequency relationship. Studies now are needed to determine the comparative sensitivity of TDI and St variables for the early detection of canine DCM.     

Alterations in vascular reactivity in isolated vessel segments from dogs with naturally occurring heart failure

To investigate if functional vascular reactivity is altered in heart failure, the reactivity of isolated canine saphenous vein (SV) and femoral artery (FA) rings, from control dogs and dogs with naturally occurring heart failure was examined. In both vessels, relaxation responses to the endothelium-dependent vasodilator, acetylcholine were unaffected by heart failure. In the FA, in heart failure, there was a significant reduction in the potency of the agonist noradrenaline (pEC(50)6.05+/-0.07 (N = 8) and 5.54 +/- 0.13 (N = 7) for control and heart failure respectively). There was no significant alteration in potency in the SV. In addition, in the FA the maximum responses to both noradrenaline (control 3.64 +/- 0.31 KPa, (N = 8); failure 5.11 +/- 0.35 KPa, (N = 7) P = 0.004) and potassium chloride (control 2.18 +/- 0.26 KPa, (N = 8); failure 4.46 +/- 0.25 KPa, (N = 7) P = 0.001) were significantly increased in heart failure. It is suggested that enhanced agonist induced responses, in the femoral artery, in dogs with heart failure, may limit blood flow to exercising skeletal muscle and subsequently reduce exercise tolerance.     

The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy

Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A contribution of serotonin to valvular disease has been reported, but myocardial expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA expression in dogs with DCM and to correlate results with expression of markers for inflammation and remodelling. Myocardial samples from eight healthy dogs, four dogs with DCM, five with cardiac diseases other than DCM and six with systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using quantitative PCR (qPCR). The results were compared to mRNA expression of selected cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and immunohistochemistry were employed to identify the cells expressing 5-HTR2B.The myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs with DCM, 5-HTR2B mRNA values were significantly greater than in all other groups, with highest levels of expression in the left ventricle and right atrium. Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs and TIMPs was observed. The findings suggest that serotonin might play a role in normal cardiac structure and function and could contribute to myocardial remodelling and functional impairment in dogs with DCM.     

Evaluation of a killed feline panleukopenia virus vaccine against canine parvoviral enteritis in dogs

Immunogenic potency of a killed feline panleukopenia virus vaccine against canine parvoviral enteritis in dogs was examined. The vaccine elicited hemagglutination-inhibition antibodies to canine parvovirus (CPV) in all of the 72 dogs which were vaccinated. The vaccine was protective in dogs against both experimentally induced and naturally occurring CPV-induced disease. By statistical analysis, 4 weeks was found to be the optimal spacing between 2 vaccinal doses resulting in hemagglutination-inhibition antibody titers up to 1:5,120. Adverse reactions to the vaccine were not observed. Atypical lymphocytes were found consistently in the CPV-infected control dogs.     

Identification of serum biomarkers for canine B-cell lymphoma by use of surface-enhanced laser desorption-ionization time-of-flight mass spectrometry

OBJECTIVE: To identify biomarker proteins for B-cell lymphoma in canine serum by use of surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry and build classification trees with multiple biomarkers that have high sensitivity and specificity for that tumor type. SAMPLE POPULATION: Sera from 29 dogs with B-cell lymphoma and 87 control dogs (approx equal numbers of healthy dogs, dogs with malignant cancers other than B-cell lymphoma, and dogs with various nonneoplastic diseases or conditions). PROCEDURES: Serum samples were fractionated chromatographically and analyzed via SELDI-TOF mass spectrometry. Peak amplitudes of the spectra from the 2 sample groups were compared to identify potential biomarker peaks, and classification trees were built by use of computer software to detect patterns formed by multiple biomarkers among SELDI data sets. RESULTS: Several biomarker protein peaks in canine serum were identified, and a classification tree was built on the basis of 3 biomarker protein peaks. With 10-fold cross-validation of the sample set, the best individual serum biomarker peak had 75% sensitivity and 86% specificity and the classification tree had 97% sensitivity and 91% specificity for the classification of B-cell lymphoma. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of biomarker proteins identified in canine serum, classification trees were constructed, which may be useful for the development of a diagnostic test for B-cell lymphoma in dogs. Further investigation is needed to determine whether these biomarkers are useful for screening susceptible dog populations or for monitoring disease status during treatment and remission of B-cell lymphoma in dogs.     

Dilated cardiomyopathy (DCM) in dogs--pathological, clinical, diagnosis and genetic aspects

Dilated cardiomyopathy (DCM) is a heart disease which is often found in humans and animals. The age of onset of this progressive disease varies between 3 and 7 years of age. A juvenile form of DCM has been found in Portuguese Water Dogs and Doberman Pinscher Dogs. Some breeds such as Doberman pinscher, Newfoundland, Portuguese Water dog, Boxer, Great Dane, Cocker Spaniel and Irish Wolfhound exhibit a higher prevalence to DCM. There also seems to be a sex predisposition as male dogs are affected more often than female dogs and in Great Danes an X-linked recessive inheritance is likely. In Newfoundland and Boxer an autosomal dominant inheritance was found whereas an autosomal recessive inheritance was described in Portuguese Water Dogs. Atrial fibrillation as a cause or consequence of DCM is assumed for certain breeds. The causes of DCM are widely unknown in dogs. A genetic basis for this heart disease seems to exist. Apart from a few exceptions the mode of inheritance and the possible underlying gene mutations are not known for DCM in dogs. In humans mutations in several genes responsible for DCM have been identified. Comparative genetic analyses in dogs using genes causing DCM in men and a genome-wide scan with anonymus markers were not able to detect causative mutations or genomic regions harboring gene loci linked to DCM. The investigation of the genetic basis of canine DCM may lead to new insights into the pathogenesis of DCM and may result in new therapeutic approaches and breeding strategies.