Research Toolkit

For researchers interested in studying MFM13, below is the list of resources currently available. While we are doing our best to make sure information in this table is up to date, please feel free to reach out to us for me most recent information.

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Cells and DNA available from Coriell Cell Repository

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Mice

1. Knock out mouse model: C57BL/6NJ-Hspb8em1(IMPC)J/Mmjax (Jackson Lab): MMRRC Strain #051194-JAX, RRID: MMRRC_051194-JAX- (Bouhy et al, 2018)

Key characteristics of the mice:

• Lack of motor or sensory phenotype or CMAP abnormalities, normal behaviour and physiology. No myopathic or neuropathic phenotype
• absence of atrophic or necrotic fibres in garstrocnemius via EM analysis
• accumulation of pathologic mitochondria many of which presented with degenerating cristae and abnormal matrix in gastrocnemius
• an increased susceptibility to heart failure under the specific context of cardiac overload (Qiu et al., 2011)

2. Partially humanized knock out model of MFM13 (in progress).

This model is being developed to closely replicate the biological processes and symptoms seen in patients with MFM13, allowing researchers to explore how the HSPB8 mutation drives disease and to test potential therapeutic strategies.

Key characteristics:

• c.515 frameshift mutation in the HSPB8 gene leading to an elongated C-terminal tail and toxic gain-of-function
• Humanized C-terminal region, with the human HSPB8 sequence introduced from nucleotide c.515

Model under development in collaboration with the International Institute of Molecular and Cell Biology (IIMCB) in Warsaw