Journal article

Altered biometal homeostasis is associated with CLN6 mRNA loss in mouse neuronal ceroid lipofuscinosis

Katja M Kanninen, Alexandra Grubman, Aphrodite Caragounis, Clare Duncan, Sarah J Parker, Grace E Lidgerwood, Irene Volitakis, George Ganio, Peter J Crouch, Anthony R White



Neuronal ceroid lipofuscinoses, the most common fatal childhood neurodegenerative illnesses, share many features with more prevalent neurodegenerative diseases. Neuronal ceroid lipofuscinoses are caused by mutations in CLN genes. CLN6 encodes a transmembrane endoplasmic reticulum protein with no known function. We characterized the behavioural phenotype of spontaneous mutant mice modeling CLN6 disease, and demonstrate progressive motor and visual decline and reduced lifespan in these mice, consistent with symptoms observed in neuronal ceroid lipofuscinosis patients. Alterations to biometal homeostasis are known to play a critical role in pathology in Alzheimer's, Parkinson's, Huntington's an..

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Awarded by Sigrid Juselius Foundation

Awarded by Academy of Finland

Awarded by Australian Research Council (ARC)

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by ARC

Funding Acknowledgements

We thank Nastasia Lim for her help with the mouse behavioural testing. This work was supported by The Sigrid Juselius Foundation [grant number 1512032 to K.M.K]; the Academy of Finland [grant number 135625 to K.M.K]; the Australian Research Council (ARC) [DP110101368]; and National Health and Medical Research Council of Australia (NHMRC) [628946]. A.R.W. is a recipient of an ARC Future Fellowship [FT100100674]. The funding sources had no influence in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.