Project description:BACKGROUND: MicroRNAs negatively regulate gene expression and play a pivotal role in the pathogenesis of human type 2 diabetes mellitus (T2DM). As the domestic cat presents a spontaneous animal model for human T2DM, the purpose of this study was to investigate whether microRNAs are detectable in feline serum and whether microRNA expression profiles differ between healthy and diabetic cats. METHODS: Total RNA was extracted from 400 µl serum of healthy lean (HL) and newly diagnosed diabetic (D) cats. MicroRNA microarrays representing 1079 distinct mouse miRNA targets were used to measure miRNA expression in samples from eight HL and eight D cats. RESULTS: By microarray, 227 distinct microRNAs were identified. Nineteen miRNAs were differentially expressed in diabetic cats, but only two reached statistical significance after correction for multiple comparisons. In qRT-PCR, miR-122* was found to be upregulated in diabetic cats more than 40-fold compared to HL cats, while miR-193b was upregulated about 10-fold. MiR-483* showed a 6- fold increase in diabetic cats compared to HL cats. CONCLUSIONS: Small volumes of serum samples yield sufficient material to detect altered microRNA expression profiles in diabetic cats. The domestic cat may be considered a useful animal model for studying miRNAs involved in human T2DM.
Project description:BACKGROUND: MicroRNAs negatively regulate gene expression and play a pivotal role in the pathogenesis of human type 2 diabetes mellitus (T2DM). As the domestic cat presents a spontaneous animal model for human T2DM, the purpose of this study was to investigate whether microRNAs are detectable in feline serum and whether microRNA expression profiles differ between healthy and diabetic cats. METHODS: Total RNA was extracted from 400 M-BM-5l serum of healthy lean (HL) and newly diagnosed diabetic (D) cats. MicroRNA microarrays representing 1079 distinct mouse miRNA targets were used to measure miRNA expression in samples from eight HL and eight D cats. RESULTS: By microarray, 227 distinct microRNAs were identified. Nineteen miRNAs were differentially expressed in diabetic cats, but only two reached statistical significance after correction for multiple comparisons. In qRT-PCR, miR-122* was found to be upregulated in diabetic cats more than 40-fold compared to HL cats, while miR-193b was upregulated about 10-fold. MiR-483* showed a 6- fold increase in diabetic cats compared to HL cats. CONCLUSIONS: Small volumes of serum samples yield sufficient material to detect altered microRNA expression profiles in diabetic cats. The domestic cat may be considered a useful animal model for studying miRNAs involved in human T2DM. Blood was drawn from two groups of cats: 8 healthy cats and 8 cats suffering from diabetes. After clotting, samples were centrifuged and total mRNA was extracted from serum. These 16 serum samples were analyzed and the groups were compared. Due to technical problems during hybridization (leaking chamber), sample 1_4_B (Serum_diabetic_8) was not included into analysis.
Project description:MicroRNAs negatively regulate gene expression and may serve as biomarkers for human cardiomyopathy. In the domestic cat, hypertrophic cardiomyopathy (HCM) represents the most common primary cardiomyopathy. In humans, the etiology of HCM is linked to mutations in genes of contractile muscle proteins, while in cats a clear proof for causal mutations is missing. The etiology of feline HCM is uncertain. Diagnosis is made by heart ultrasound examination and measuring the serum level of N-terminal pro B-type natriuretic peptide. The purpose of this study was to investigate whether microRNA profiles in the serum of cats with HCM are different from the profiles of healthy cats and whether specific miRNAs can be detected to serve as potential biomarkers for feline HCM or may help in understanding the etiology of this disease Blood was drawn from two groups of cats: 12 healthy cats and 11 cats suffering from hypertrophic cardiomyopathy. After clotting, samples were centrifuged and total mRNA was extracted from serum. These 23 serum samples were analyzed and the groups were compared
Project description:MicroRNAs negatively regulate gene expression and may serve as biomarkers for human cardiomyopathy. In the domestic cat, hypertrophic cardiomyopathy (HCM) represents the most common primary cardiomyopathy. In humans, the etiology of HCM is linked to mutations in genes of contractile muscle proteins, while in cats a clear proof for causal mutations is missing. The etiology of feline HCM is uncertain. Diagnosis is made by heart ultrasound examination and measuring the serum level of N-terminal pro B-type natriuretic peptide. The purpose of this study was to investigate whether microRNA profiles in the serum of cats with HCM are different from the profiles of healthy cats and whether specific miRNAs can be detected to serve as potential biomarkers for feline HCM or may help in understanding the etiology of this disease
Project description:Cats frequently develop myocardial remodelling, for example, hypertrophic cardiomyopathy, affecting 14.7 percent of domestic cats compared to 0.2 percent of humans, with shared genetic features making them relevant to human disease. Yet features distinguishing clinical outcomes such as heart failure and arterial thromboembolism remain poorly characterized. Using artificial intelligence-based digital pathology and Oxford Nanopore sequencing, we analyzed myocardial tissue from 37 cats grouped by outcome: arterial thromboembolism, congestive heart failure, or no documented cardiac disease. Myocardial fibrosis was significantly higher in cats with arterial thromboembolism, indicating a distinct fibrotic phenotype. Cats with heart failure showed nuclear hypertrophy, while cats with arterial thromboembolism had increased numbers of small, hematoxylin-dense non-myocyte nuclei. Higher fibrosis was associated with downregulation of mitochondrial and cardiac conduction genes, and nuclear size correlated with proteostasis and stress-response pathways. This multimodal framework reveals distinct histological and molecular profiles by outcome, with relevance for translational hypertrophic cardiomyopathy research.
2026-06-05 | GSE296746 | GEO
Project description:RADseq of domestic cats, Asian leopard cats, and domestic cat hybrids
Project description:The aim with this study was to evaluate the miRNA-transcriptome in whole blood in cats with or without pre-clinical HCM. Twelve age, sex and breed matched cats were included. Six cats were Norwegian forest cats and six were domestic mixed breed cats. Each breed represented with three healthy and three preclinical cats. The intention was to evaluate if there were differences in miRNA-profiles between healthy and affected cats, but also to evaluate breed differences and which potential targets the identified miRNAs might have. Bioinformatical pipeline included: bcl2fastq was used to convert sequence files to fastq-format. CutAdapt for adapter and sequence quality trimming, statification and quality evaluation with STAR, FastQC and MultiQC, followed by miRNA-prediction in miRDeep2. Human miRNA-sequences were used as main reference, along with mouse and dog as additional references. Predicted miRNAs were further evaluated for data stratification in DESeq2, followed by differential evaluation analyses based on single or more complex group models (includinig initeraction model). For target prediction IntaRNA was used to identify potential gene transcripts targeted in the feline genome, based on exported feline 3'UTR-sequences from Ensemble. As a comparison human targets were evaluated based on lists in miRDB, since miRNAs are usually conserved between species and the feline genome is less well annotated compared to the human. The results highlighted the importance of considering breed differences when evaluating circulating miRNAs in feline whole blood. This is of high relevance for studies trying to identify miRNAs as potential biomarkers. Also, our results only identified one miRNA differentially expressed between healthy and pre-clinical HCM cats within the Norwegian Forest cats, also highlighting breed differences. One reason for only identifying one miRNA may be that the cats were in pre-clinical state, instead of in congestive heart failure.
Project description:Purpose: Photoperiod is known to cause physiological changes in seasonal mammals, including body weight, physical activity, and reproductive status. Because cats are seasonal breeders, we recently tested the effects of day length on resting metabolic rate, voluntary physical activity, and food intake. In that study, resting metabolic rate, physical activity, and food intake to maintain body weight were greater in cats exposed to long days vs. short days. Because photoperiod has also been demonstrated to affect adipose tissue gene expression in several species, including dairy cows, sheep, and Siberian hamsters, the objective of this study was to determine the effects of day length on the adipose transcriptome profile of cats as assessed by RNA-seq. Methods: Ten healthy adult neutered male domestic shorthair cats were used in a randomized crossover design study. During two 12-wk periods, cats were exposed to either short days (8 hr light:16 hr dark) or long days (16 hr light:8 hr dark). Cats were fed a commercial diet to maintain baseline body weight. Subcutaneous adipose biopsies were collected at wk 12 of each period for RNA isolation and Illumina sequencing. Results: A total of 578 million sequences (28.9 million/sample) were generated by Illumina sequencing. Using a raw p value of P<0.005, 170 mRNA transcripts were differentially expressed between short day- and long day-housed cats. Of the 170 transcripts highlighted, 25 annotated transcripts were up-regulated, while 116 annotated transcripts were down-regulated by long days. Another 29 un-annotated transcripts (name and function not known) were also different between groups. In general, adipose tissue of long day-housed cats had greater expression of genes involved with cholesterol trafficking, fatty acid synthesis and immune function, and lower expression of genes involved with cell cycle and growth, cell development and structure, and protein processing, when compared to short day-housed cats. Subcutaneous adipose tissue mRNA profiles of healthy adult neutered male cats exposed to short days (8 hr light: 16 hr dark) or long days (16 hr light: 8 hr dark) using Illumina sequencing.