The mdx Mutation in the 129/Sv Background Results in a Milder Phenotype: Transcriptome Comparative Analysis Searching for the Protective Factors.

The mdx mouse is a good genetic and molecular murine model for Duchenne Muscular Dystrophy (DMD), a progressive and devastating muscle disease. However, this model is inappropriate for testing new therapies due to its mild phenotype. Here, we transferred the mdx mutation to the 129/Sv strain with the aim to create a more severe model for DMD. Unexpectedly, functional analysis of the first three generations of mdx129 showed a progressive amelioration of the phenotype, associated to less connective tissue replacement, and more regeneration than the original mdxC57BL. Transcriptome comparative analysis was performed to identify what is protecting this new model from the dystrophic characteristics. The mdxC57BL presents three times more differentially expressed genes (DEGs) than the mdx129 (371 and 137 DEGs respectively). However, both models present more overexpressed genes than underexpressed, indicating that the dystrophic and regenerative alterations are associated with the activation rather than repression of genes. As to functional categories, the DEGs of both mdx models showed a predominance of immune system genes. Excluding this category, the mdx129 model showed a decreased participation of the endo/exocytic pathway and homeostasis categories, and an increased participation of the extracellular matrix and enzymatic activity categories. Spp1 gene overexpression was the most significant DEG exclusively expressed in the mdx129 strain. This was confirmed through relative mRNA analysis and osteopontin protein quantification. The amount of the 66 kDa band of the protein, representing the post-translational product of the gene, was about 4,8 times higher on western blotting. Spp1 is a known DMD prognostic biomarker, and our data indicate that its upregulation can benefit phenotype. Modeling the expression of the DEGs involved in the mdx mutation with a benign course should be tested as a possible therapeutic target for the dystrophic process.

Valores de pressão arterial de cães da raça Golden Retriever clinicamente sadios / Blood pressure levels in clinically healthy Golden Retriever

A hipertensão arterial sistêmica é uma enfermidade que afeta tanto cães quanto gatos e apresenta grande importância na prática da clínica veterinária. É caracterizada pelo aumento sustentado da pressão arterial sistêmica sistólica e/ou diastólica e pode levar a consequências deletérias, principalmente em rins, coração, olhos e sistema nervoso central. Diferentes estudos já foram realizados para a avaliação de técnicas de medida da pressão arterial em cães, comparando diferentes técnicas, com animais em diversos estados de consciência e em diferentes posições. A faixa de normalidade pode variar fisiologicamente nos cães, principalmente de acordo com a raça, sexo, idade, temperamento, condições patológicas, exercícios e dieta. Sabendo-se que o Golden Retriever pode apresentar distrofia muscular canina ligada ao cromossomo X e pode desenvolver cardiomiopatia dilatada e hipertensão sistêmica, no presente estudo, fez-se a mensuração da pressão arterial (por meio de dispositivo de Doppler) em 38 cães clinicamente sadios da referida raça com o propósito de obter parâmetros cardiovasculares que possam servir de referência. A partir dos resultados, pôde-se concluir que alterações significativas no peso corpóreo, principalmente dos três aos seis meses de idade, influenciam nos valores de pressão arterial; que a pressão arterial sistólica é maior em machos do que em fêmeas; e que os valores de pressão arterial são variáveis dentro de uma mesma raça canina.

Arterial hypertension is a disease that affects both dogs and cats and presents great importance in veterinary clinic practice. It is characterized by sustained increase in systolic blood pressure systemic and / or diastolic and can cause deleterious consequences, especially in kidney, heart, eyes and central nervous system. Different studies have been conducted for the evaluation of techniques for measuring blood pressure in dogs, comparing different techniques, with animals in various states of consciousness and in different positions. The range of normality can vary physiologically in dogs, mainly according to breed, sex, age, temperament, pathological conditions, exercise and diet. Knowing that the Golden Retriever can submit muscular dystrophy canine linked to chromosome X and can develop dilated cardiomyopathy and systemic hypertension, in this study, the blood pressure (with Doppler) of 38 clinically healthy dogs of that breed was measure with the purpose to obtain parameters that could serve as a reference. From the results, we concluded that significant changes in body weight, mainly from three to six months, influence the blood pressure values, whereas systolic blood pressure is higher in males than in females, and that the pressure values pressure are variables within the same breed of dog.