A dystonia-like movement disorder with brain and spinal neuronal defects is caused by mutation of the mouse laminin β1 subunit, Lamb1

Yi Bessie Liu, Ambika Tewari, Johnny Salameh, Elena Arystarkhova, Thomas G. Hampton, Allison Brashear, Laurie J. Ozelius, Kamran Khodakhah, Kathleen J. Sweadner

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

A new mutant mouse (lamb1t) exhibits intermittent dystonic hindlimb movements and postures when awake, and hyperextension when asleep. Experiments showed co-contraction of opposing muscle groups, and indicated that symptoms depended on the interaction of brain and spinal cord. SNP mapping and exome sequencing identified the dominant causative mutation in the Lamb1 gene. Laminins are extracellular matrix proteins, widely expressed but also known to be important in synapse structure and plasticity. In accordance, awake recording in the cerebellum detected abnormal output from a circuit of two Lamb1-expressing neurons, Purkinje cells and their deep cerebellar nucleus targets, during abnormal postures. We propose that dystonia-like symptoms result from lapses in descending inhibition, exposing excess activity in intrinsic spinal circuits that coordinate muscles. The mouse is a new model for testing how dysfunction in the CNS causes specific abnormal movements and postures.

Original languageEnglish (US)
Article numbere11102
JournaleLife
Volume4
Issue numberDECEMBER2015
DOIs
StatePublished - Dec 24 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Liu, Y. B., Tewari, A., Salameh, J., Arystarkhova, E., Hampton, T. G., Brashear, A., Ozelius, L. J., Khodakhah, K., & Sweadner, K. J. (2015). A dystonia-like movement disorder with brain and spinal neuronal defects is caused by mutation of the mouse laminin β1 subunit, Lamb1. eLife, 4(DECEMBER2015), [e11102]. https://doi.org/10.7554/eLife.11102