Spatiotemporal expression pattern of KIF21A during normal embryonic development and in congenital fibrosis of the extraocular muscles type 1 (CFEOM1)
Congenital fibrosis of the extraocular muscles type 1 (CFEOM1) is a rare inherited strabismus syndrome characterized by non-progressive ophthalmoplegia. We previously identified that CFEOM1 results from heterozygous missense mutations in KIF21A, which encodes a kinesin motor protein. Here we evaluate the expression pattern of KIF21A in human brain and muscles of control and CFEOM1 patients, and during human and mouse embryonic development. KIF21A is expressed in the cell bodies, axons, and dendrites of many neuronal populations including those in the hippocampus, cerebral cortex, cerebellum, striatum, and motor neurons of the oculomotor, trochlear, and abducens nuclei from early development into maturity, and its spatial distribution is not altered in the CFEOM1 tissues available for study.Multiple splice isoforms of KIF21A are identified in human fetal brain, but none of the reported CFEOM1 mutations are located in or near the alternatively spliced exons. KIF21A immunoreactivity is also observed in extraocular and skeletal muscle biopsies of control and CFEOM1 patients, where it co-localizes with triadin, a marker of the excitation-contractile coupling system. The diffuse and widespread expression of KIF21A inthe developing human and mouse central and peripheral nervous system as well as in extraocular muscledoes not account for the restricted ocular phenotype observed in CFEOM1, nor does it permit the formal exclusion of a myogenic etiology based on expression patterns alone. âº KIF21Ais widely expressed in embryonic and adulthuman and mouse neurons and muscles. âº KIF21A co-localizes with triadin in skeletal and extraocular muscles. âº KIF21A spatial expression pattern in CFEOM1 does not vary from control tissues. âº KIF21A expression pattern does not account for the restricted CFEOM1 phenotype.