Murine succinate semialdehyde dehydrogenase (SSADH) deficiency, a heritable disorder of GABA metabolism with epileptic phenotype

IUBMB Life. 2005 Sep;57(9):639-44. doi: 10.1080/15216540500264588.

Abstract

Murine models of inborn errors of metabolism represent an established approach for investigating pathophysiological mechanisms associated with the corresponding human disorder. Our laboratory studies human inherited defects of GABA synthesis and degradation. One of these, succinate semialdehyde dehydrogenase (SSADH) deficiency (or gamma-hydroxybutyric aciduria; OMIM 271980; E.C. 1.2.1.24), has recently been modeled via gene targeting in the mouse. SSADH-/- mice succumb to early lethality in status epilepticus at postnatal (PN) days 20 - 26. Numerous metabolic, neurochemical and neurophysiological abnormalities have been documented using in vitro and in vivo approaches, substantially altering our thoughts about the complexity of the corresponding human condition. Moreover, novel preclinical treatment paradigms have been developed through drug trials in gene-ablated animals. The greatest utility of this animal, however, may reside in its transition from early absence seizures to generalized convulsions and eventual status epilepticus. Accurate neurochemical assessment during this transition may provide clues to the same transition process in patients, for which the underlying mechanisms remain undefined.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Epilepsy, Absence / drug therapy
  • Epilepsy, Absence / enzymology*
  • Humans
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism*
  • Metabolism, Inborn Errors / pathology
  • Mice
  • Mice, Knockout
  • Phenotype*
  • Succinate-Semialdehyde Dehydrogenase / deficiency*
  • Succinate-Semialdehyde Dehydrogenase / metabolism
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • gamma-Aminobutyric Acid
  • Succinate-Semialdehyde Dehydrogenase