Mottled Mice and Non-Mammalian Models of Menkes Disease

Lenartowicz, Małgorzata; Krzeptowski, Wojciech; Lipiński, Paweł; Grzmil, Paweł; Starzyński, Rafał R.; Pierzchała, Olga; Møller, Lisbeth Birk

doi:10.3389/fnmol.2015.00072

Cited by 25 publications

(26 citation statements)

References 160 publications

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“…The murine gene locus Atp7a and the human homolog ATP7A are located on the X chromosome, and share >80% homology. Both gene products on sequence alignment show highly conserved amino acid sequences within functional domains 97. These similarities extend to the ATP7A proteins in zebrafish and fruitfly.…”

Section: Animal Modelsmentioning

confidence: 71%

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Menkes disease: what a multidisciplinary approach can do

Ojha¹,

Prasad²

2016

JMDH

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Disorders of copper homeostasis are currently recognized across the life span. Their recognition and links to human disease have spanned several decades, beginning with the recognition of a degenerative disorder in the offspring of sheep grazing in copper-deficient pastures, through to the description of infants suffering from a progressive neurodegenerative disorder characterized by epileptic seizures, developmental regression, failure to thrive, and an unusual hair quality (giving the condition its distinctive label of “kinky hair disease”). In this review, we trace the historical background and describe the biochemistry and physiology of copper metabolism and transport, inheritance patterns, molecular genetics, and genotype–phenotype correlations based on current understanding of the disorder. It is clear from the clinical presentations and variants that disorders of copper homeostasis include phenotypes ranging from mild occipital horn syndrome to intermediate and severe forms of classical Menkes disease. The symptoms involve multiple organ systems such as brain, lung, gastrointestinal tract, urinary tract, connective tissue, and skin. A multisystem disorder needs a multidisciplinary approach to care, as treatment interventions permit longer survival for some individuals. Animal models have been developed to help screen treatment options and provide a better understanding of these disorders in the laboratory. Finally, we propose a multidisciplinary approach to promote continued research (both basic and clinical) to improve survival, quality of life, and care for these conditions.

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Section: Animal Modelsmentioning

confidence: 71%

“…A detailed assessment of these mutants is beyond the scope of this review. The reader is referred to an outstanding review on the subject 97. It is however important to summarize important insights that have been gained.…”

Section: Animal Modelsmentioning

confidence: 99%

Menkes disease: what a multidisciplinary approach can do

Ojha¹,

Prasad²

2016

JMDH

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“…Small animal models are relatively inexpensive and can provide a wealth of information about key physiological processes and suggest disease mechanisms (Lenartowicz et al . ). Figure demonstrates the evolutionary relationship of the copper‐transporting P‐type ATPases of commonly used animal models for human disease.…”

Section: Caenorhabditis Elegans Drosophila and Danio Reriomentioning

confidence: 97%

Animal models of Wilson disease

Reed

Lutsenko²,

Bandmann

2018

Journal of Neurochemistry

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Wilson disease (WD) is an autosomal recessive disorder of copper metabolism manifesting with hepatic, neurological and psychiatric symptoms. The limitations of the currently available therapy for WD (particularly in the management of neuropsychiatric disease), together with our limited understanding of key aspects of this illness (e.g. neurological vs. hepatic presentation) justify the ongoing need to study WD in suitable animal models. Four animal models of WD have been established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b knockout mouse and the Labrador retriever. The existing models of WD all show good similarity to human hepatic WD and have been helpful in developing an improved understanding of the human disease. As mammals, the mouse, rat and canine models also benefit from high homology to the human genome. However, important differences exist between these mammalian models and human disease, particularly the absence of a convincing neurological phenotype. This review will first provide an overview of our current knowledge of the orthologous genes encoding ATP7B and the closely related ATP7A protein in C. elegans, Drosophila and zebrafish (Danio rerio) and then summarise key characteristics of rodent and larger mammalian models of ATP7B-deficiency.

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“…For clarification of the pathology and development of new treatment of MD, various types of mice with a mutation in the mottled gene (atp7a) are used as MD model (Lenartowicz et al 2015). Macular mice possess a mutation in the atp7a gene and have a clinical phenotype and biochemical abnormalities similar to MD patients (e.g., severe neurodegeneration and kinky hair) (Kodama et al 1991;Mori and Nishimura 1997;Murata et al 1997).…”

Section: Introductionmentioning

confidence: 99%