Adult-onset autosomal-dominant leukodystrophy (ADLD) is a progressive and fatal neurological disorder characterized by early autonomic dysfunction, cognitive impairment, pyramidal tract and cerebellar dysfunction, and white matter loss in the central nervous system. ADLD is caused by duplication of the LMNB1 gene, which results in increased lamin B1 transcripts and protein expression.
This transgenic strain expresses human Lmnb1 from a FLAG-tagged tetracycline-responsive element (TRE). When crossed with animals expressing the tetracycline-controlled transactivator (tTA) or reverse tetracycline-controlled transactivator (rtTA) protein under the control of tissue-specific promoters, transgene expression can be regulated in the offspring by the administration of doxycycline.
When crossed with an Camk2a-tTA strain (see Stock No. 003010), LMNB1 is overexpressed specifically in neurons. When crossed with an GFAP-tTA strain (e.g. Stock No. 005964), LMNB1 is overexpressed specifically in astrocytes. Compound mutant mice show no motor deficits on the balance beam and accelerated rotarod at 12 months and no overt behavioral abnormalities beyond 1 year.
