Sensory-motor circuit is a therapeutic target for mice, a model of hereditary sensory and autonomic neuropathy 6.

Mutations in Dystonin (), which encodes cytoskeletal linker proteins, cause hereditary sensory and autonomic neuropathy 6 (HSAN-VI) in humans and the () phenotype in mice; however, the neuronal circuit underlying the HSAN-VI and phenotype is unresolved. mice exhibit dystonic movements accompanied by the simultaneous contraction of agonist and antagonist muscles and postnatal lethality. Here, we identified the sensory-motor circuit as a major causative neural circuit using a gene trap system that enables neural circuit-selective inactivation and restoration of by Cre-mediated recombination.

Attenuated cerebellar phenotypes in Inpp4a truncation mutants with preserved phosphatase activity.

Phosphoinositides (PIPs) act as intracellular signaling molecules that regulate various cellular processes. Abnormalities in PIP metabolism cause various pathological conditions, including neurodegenerative diseases, cancer and immune disorders. Several neurological diseases with diverse phenotypes, such as ataxia with cerebellar atrophy or intellectual disability without brain malformation, are caused by mutations in INPP4A, which encodes a phosphoinositide phosphatase.

Isoform-specific mutation in Dystonin-b gene causes late-onset protein aggregate myopathy and cardiomyopathy.

Dystonin (), which encodes cytoskeletal linker proteins, expresses three tissue-selective isoforms: neural DST-a, muscular DST-b, and epithelial DST-e. mutations cause different disorders, including hereditary sensory and autonomic neuropathy 6 (HSAN-VI) and epidermolysis bullosa simplex; however, etiology of the muscle phenotype in -related diseases has been unclear. Because contains all of the -encoding exons, known HSAN-VI mutations could affect both DST-a and DST-b isoforms.