当前位置： SCI文献检索 > JOURNAL OF NEUROSCIENCE RESEARCH期刊下所有文献 > Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice.

Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice.

Abstract：

:In its severe form, X-linked adrenoleukodystrophy (ALD) is a lethal neurologic disease of children, characterized by progressive cerebral demyelination and adrenal insufficiency. Associated with a biochemical defect of peroxisomal beta-oxidation, very long-chain fatty acids (VLCFA) build up in tissues that have a high turnover of lipids, such as central nervous system (CNS) white matter, adrenal cortex, and testis. Whether the abnormal accumulation of VLCFA is the underlying cause of demyelination or merely an associated biochemical marker is unknown. ALD is caused by mutations in the gene for a peroxisomal membrane protein (ALDP) that shares structural features with ATP-binding-cassette (ABC) transporters. To analyze the cellular function of ALDP and to obtain an animal model of this debilitating disease, we have generated transgenic mice with a targeted inactivation of the ald gene. Motor functions in ALDP-deficient mice developed at schedule, and unexpectedly, adult animals appeared unaffected by neurologic symptoms up to at least 6 months of age. Biochemical analyses demonstrated impaired beta-oxidation in mutant fibroblasts and abnormal accumulation of VLCFAs in the CNS and kidney. In 6-month-old mutants, adrenal cortex cells displayed a ballooned morphology and needle-like lipid inclusions, also found in testis and ovaries. However, lipid inclusions and demyelinating lesions in the CNS were not a feature. Thus, complete absence of ALDP expression results in a VLCFA storage disease but does not impair CNS function of young adult mice by pathologic and clinical criteria. This suggests that additional genetic or environmental conditions must be fulfilled to model the early-onset and lethality of cerebral ALD in transgenic mice.

journal_name

J Neurosci Res

journal_title

Journal of neuroscience research

authors

Forss-Petter S,Werner H,Berger J,Lassmann H,Molzer B,Schwab MH,Bernheimer H,Zimmermann F,Nave KA

doi

10.1002/(SICI)1097-4547(19971201)50:5<829::AID-JNR

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

829-43

issue

eissn

0360-4012

issn

1097-4547

pii

10.1002/(SICI)1097-4547(19971201)50:5<829::AID-JNR

journal_volume

pub_type

杂志文章

在线工具

Targeted inactivation of the X-linked adrenoleukodystrophy gene in mice.