HEX DEFICIENIES: BIOCHEMICAL &MOLECULAR GENETICS

Project Details

Description

Hexosaminidase (HEX) deficiency causes several neurological
disease phenotypes including spinal muscular atrophy and an ALS-
like disorder in adults, cerebellar ataxia in children, and in infants
dementia, seizures, and retinopathy. At least three gene loci are
required for full HEX activity and defects at each can cause
disease. This project is focused on defining the specific gene defects and
peptide defects in our large group of patients with HEX
deficiency disease. For the most part we will study patients'
fibroblasts in culture. We have transformed with SV-40 a large
group of HEX deficient patients' fibroblasts cultured from skin.
Defects of regulatory genes cannot be easily studied in humans at
present. Therefore, we have turned to the best available
mammalian system, inbred mice, to study HEX regulation,
especially temporal regulation, which may be important for some
of our late-onset HEX deficient patients. We plan to compare
HEX cDNA sequences and later genomic sequences from two
inbred mouse strains which show genetically determined
differences in HEX expression. We are taking advantage of four new tools which we have
developed: 1. A new system for study HEX regulation,
2. A new method of peptide mapping using in situ CNBr cleavage,
3. Anti-HEX beta subunit monoclonal antibodies we recently
raised, so far as we know the first anti-HEX monoclonals made,
4. A unique HEX beta-gene sequence which we recently cloned
and have characterized.
StatusFinished
Effective start/end date3/1/796/30/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)
  • Neuroscience(all)

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