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Murine succinate semialdehyde dehydrogenase (SSADH) deficiency, a heritable disorder of GABA metabolism with epileptic phenotype
Author(s) -
Gibson K. M.,
Jakobs C.,
Pearl P. L.,
Snead O. C.
Publication year - 2005
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216540500264588
Subject(s) - neurochemical , status epilepticus , phenotype , biology , epilepsy , in vivo , metabolic disorder , neuroscience , biochemistry , gene , genetics
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.IUBMB Life, 57: 639‐644, 2005