Hereditary spastic paraplegia development associated with changes in endoplasmic reticulum

September 24, 2013

Hereditary spastic paraplegias (HSP) are a group of hereditary diseases that result in progressive loss of motor function in the lower limbs, and mutations in many different genes have been implicated in disease progression. One common feature of HSP is the progressive degradation of the axons of cortical motor neurons; however, it is not fully understood how mutations in is so many different genes result in axonal degradation.

In this issue of the Journal of Clinical Investigation, Christian Hübner and colleagues at Jena University develop a mouse model of HSP by introducing a human-associated mutation into the gene encoding receptor accessory protein 1 (REEP1). Mice with this Reep1 mutation exhibited age-dependent loss of motor function and axonal degradation in the spinal cord.

The authors revealed a role for REEP1 in maintaining the shape of the endoplasmic reticulum (ER) and changes in ER structure associated with Reep1 mutations might impair ER function.

In the companion commentary, Ariel Deutch and colleagues at Vanderbilt University discuss how this new will be useful for understanding the how changes in ER morphology result in HSP-associated axon loss.

Explore further: Spasticity gene finding provides clues to causes of nerve cell degeneration

More information: A spastic paraplegia mouse model reveals REEP1-dependent ER shaping, J Clin Invest. 2013;123(10):4273–4282. DOI: 10.1172/JCI65665
REEPing the benefits of an animal model of hereditary spastic paraplegia, J Clin Invest. 2013;123(10):4134–4136. DOI: 10.1172/JCI72324

Related Stories

Spasticity gene finding provides clues to causes of nerve cell degeneration

January 9, 2012
The discovery of a gene that causes a form of hereditary spastic paraplegia (HSP) may provide scientists with an important insight into what causes axons, the stems of our nerve cells, to degenerate in conditions such as ...

Researchers untangle molecular pathology of giant axonal neuropathy

April 15, 2013
Giant axonal neuropathy (GAN) is a rare genetic disorder that causes central and peripheral nervous system dysfunction. GAN is known to be caused by mutations in the gigaxonin gene and is characterized by tangling and aggregation ...

Gene required for nerve regeneration identified

November 1, 2012
A gene that is associated with regeneration of injured nerve cells has been identified by scientists at Penn State University and Duke University. The team, led by Melissa Rolls, an assistant professor of biochemistry and ...

Study offers new clues about hereditary spastic paraplegia

July 8, 2011
(Medical Xpress) -- New research from Rice University and Italy's Eugenio Medea Scientific Institute is yielding clues about hereditary spastic paraplegia (HSP), a group of inherited neurological disorders that affect about ...

Recommended for you

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

Newly discovered gene variants link innate immunity and Alzheimer's disease

July 17, 2017
Three new gene variants, found in a genome wide association study of Alzheimer's disease (AD), point to the brain's immune cells in the onset of the disorder. These genes encode three proteins that are found in microglia, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.