Introduction: Heart failure (HF) is the inability of the left ventricle to fill with or eject blood. It often occurs as a side-effect of cardiovascular complications such as ischemia. At the molecular level, Signal Transducer and Activator of Transcription 3 (STAT3) is linked to HF, as STAT3 deficient (STAT3 KO) mouse models have shown development of HF with age. Hypothesis: In a mouse model, induction of heart failure consecutive to a deletion in the STAT3 gene depends on the locus of the splice-site in the gene. Material and methods: STAT3 KO and wildtype (WT) mice were aged to provoke heart failure. Mice were anesthetised for all aspects of this experiment by intraperitoneal injection of Sodium Pentobarbitone (50mg/kg body weight) . A sufficient degree of anaesthesia was considered to be obtained in the absence of the pedal reflex, after which the chest cavity was opened, and hearts were excised. Mitochondrial respiration was measured in aged hearts using permeabilized heart fibres and an oxygen-sensing Clarke-type electrode, with fatty acids (FA) as a substrate (n=4 per group). Inability to respire with FA is a typical metabolic state of a failing heart. Histology staining (picrosirius stain) was also performed on these aged mouse hearts to quantify fibrosis, a marker for heart failure (n=6 KO, n=4 WT). Results: No significant differences detected in mitochondrial respiration using a FA substrate, indicating similar metabolic profiles in both groups (see Figure 1, p>0.05). Failing hearts exposed to FA should have shown impaired mitochondrial respiration. Histology staining for fibrosis in the aged STAT3 KO hearts showed minimal fibrosis, similar to WT hearts (KO 0.83±0.203% and WT 0.57±0.104%, p> 0.05), demonstrating no overt heart failure. All data was expressed as mean ± SEM. An unpaired student’s t-test was used for all statistical analysis. Conclusion: The STAT3 KO mouse model in our laboratory presents a different phenotype with aging compared to other published STAT 3 KO mouse models. This may be due to the location of the splicing in the STAT3 gene and the possibility of aberrant STAT3 proteins which contribute to HF in certain models, but not in others. It would therefore appear that the tendency to heart failure in STAT3 KO mice is dependent on the position of the deletion or the duration of aging.