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Mitochondrial diseases represent the most common inherited neurometabolic disorders, for which no effective therapy currently exists for most patients. The unmet clinical need requires a more comprehensive understanding of the disease mechanisms and the development of reliable and robust in vivo models that accurately recapitulate human disease. This review aims to summarise and discuss various mouse models harbouring transgenic impairments in genes that regulate mitochondrial function, specifically their neurological phenotype and neuropathological features. Ataxia secondary to cerebellar impairment is one of the most prevalent neurological features of mouse models of mitochondrial dysfunction, consistent with the observation that progressive cerebellar ataxia is a common neurological manifestation in patients with mitochondrial disease. The loss of Purkinje neurons is a shared neuropathological finding in human post-mortem tissues and numerous mouse models. However, none of the existing mouse models recapitulate other devastating neurological phenotypes, such as refractory focal seizures and stroke-like episodes seen in patients. Additionally, we discuss the roles of reactive astrogliosis and microglial reactivity, which may be driving the neuropathology in some of the mouse models of mitochondrial dysfunction, as well as mechanisms through which cellular death may occur, beyond apoptosis, in neurons undergoing mitochondrial bioenergy crisis. [ABSTRACT FROM AUTHOR]

Murine orthotopic cancer models often require surgery, potentially causing pain or distress. However, analgesics are often withheld because they may alter tumour development. Two orthotopically implanted cancers were investigated in mice pre-treated with meloxicam (10 mg/kg), buprenorphine (0.2 mg/kg) or saline (1 ml/kg). Tumours were imaged and welfare was assessed using body weight, behaviour and nociceptive responses. In study 1, BALB/c mice were inoculated with 4T1 mammary carcinoma or saline during surgery or anaesthesia. As pre-treatment with a single buprenorphine dose appeared beneficial to cancer growth consistency, a second cohort of mice additionally received saline or buprenorphine at 12 and 24 h. Surgery resulted in increased mammary tumour growth and lung metastases. These unwanted effects were lessened by buprenorphine pre-treatment, especially when given repeatedly. Mammary tumour-bearing mice became less active and nociceptive thresholds declined over time, indicating some discomfort as tumours grew. In study 2, C57BL/6 mice received B16 melanoma. This non-surgical model was used to determine whether meloxicam or buprenorphine affected cancer seeding of the lungs. While meloxicam reduced B16 lung seeding, buprenorphine did not. Mechanical thresholds decreased as cancer developed in mice bearing melanoma, but the magnitude of this was insufficient to conclude that there were any significant welfare concerns. This study highlights the scientific value in utilising non-surgical models, where possible. When surgery must be performed at the time of tumour inoculation, the effects of this should be controlled with appropriate analgesics to enhance the value and possibly translation of the research. [ABSTRACT FROM AUTHOR]