Mutant SPTLC1

Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an agedependent neuropathy.
Submitted By: Ellen Burns, Medical Liaison

The very impressive title is the name of an article published in Human Molecular Genetics, 2005, Vol. 14, No. 22. pages 3507-3521.

The primary author of this publication is Alexander McCampbell, who is responsible for the development of the mouse model for HSN-1. Others whose expertise contributed to the report include Dr. Robert H. Brown, Junior, Director of the Day Laboratory for Neuromuscular Research, Charlestown, Massachusetts and Dr. Teresa M. Dunn, Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.

Mutations in enzymes involved in sphingolipid metabolism cause a variety of neurological disorders, but how this happens, at the cellular level, is not known.

A mutated gene has been associated with HSN-1. It is identified as SPTLC1. Genes make proteins; proteins make enzymes. SPTLC1 encodes one subunit of the serine palmitoyltransferase enzyme (SPT), the rate-limiting enzyme in sphingolipid synthesis. This enzyme is known to affect the production of a fatty substance (glycosyl ceramide) in the body. HSN-1 patients have reduced SPT activity.

As we know, hereditary sensory and autonomic neuropathy type one (HSN-1) is

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Presentation: Mouse Model

Disease Research Report
Submitted by: Ellen Burns, Medical Liaison

Paper Presentation: Mouse Model for Hereditary Sensory Neuropathy Type I

Alex McCampbell, working in the Day Laboratory for Neuromuscular Research, presented a paper on hereditary sensory neuropathy in late 2004 at the Society for Neuroscience. Alex has been working for several years with Dr. Bob Brown, Jr., who is the Director of the Day Lab. Alex has been working to develop a strain of mice who demonstrate the defective gene found in the human form of HSN-1. Once referred to as the “Deater Disease,” HSN-1 is now known to be the most common hereditary disorder primarily affecting peripheral sensory neurons.

The gene with the mutations associated with HSN-1 is identified as SPTLC1. Genes make proteins; proteins make enzymes. SPTLC1 encodes one subunit of the serine palmitoyltransferase enzyme (SPT). This enzyme is known to affect the production of a fatty substance (glycosyl ceramide) in the body. Alex altered the genetic makeup of mice in several ways. He created transgenic mice. One group of mice have the mutated gene that is associated with HSN-1 added. The other group of mice was altered to over express the normal gene. The two groups were created

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