Finnish Disease Heritage in modelling rare diseases

Generation of knockout mice has greatly facilitated understanding of essential genetic requirements for life.

However, human diseases are disappointingly seldom recapitulated in knockout mice and thus they have served as inadequate in vivo models for human monogenic diseases. The next task in the field of in vivo model organisms is to generate human disease causing specific mutations in animal models. Through a national pilot project aiming at modeling the selected Finnish Heritage Diseases in mice (FinnDisMice) we are committed to utilize CRISPR/Cas9 genome editing in mimicking two rare human fetal syndromes, lethal congenital contracture syndrome (LCCS1) and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) and an adult-onset motoneuron disease the Jokela type of spinal muscular atrophy in animal models. Generation of these new in vivo disease models is expected to facilitate development of diagnostic, prognostic and therapeutic strategies not only for thee specific diseases but also advance understanding the pathomechanisms of more common diseases affecting the same cell and tissue types, such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease and other degenerative disorders.