This transgenic model of adult-onset autosomal-dominant leukodystrophy (ADLD) expresses four times the normal levels of full-length mouse Lmnb1 under the control of the endogenous promoter and regulatory sequences. Mice exhibit cognitive impairment and epilepsy, followed by age-dependent motor deficits.
Ying-Hui Fu, University of California, San Francisco
Louis Ptacek, University of California, San Francisco
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inserted expressed sequence) |
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 model of ADLD expresses four times the normal levels of full-length mouse Lmnb1 under the control of the endogenous promoter and regulatory sequences. Expression levels are approximately 4-fold higher compared with wildtype.
Animals are born healthy and are overtly indistinguishable from control littermates, but eventually recapitulate many of the features of ADLD. Mice exhibit cognitive impairment and epilepsy, followed by age-dependent motor deficits.
Substantial spatial memory deficits are observed at 12 months of age in a Morris water maze assay and exhibit impairments in a step-through passive avoidance task, which reflects long-term spatial associative learning and fear memory of an aversive experience. Transgenic animals exhibit progressive motor impairment on 2 different motor tasks, the accelerated rotarod (at 24 months of age) and balance beam (progressing at 12 months).
Frequent behavioral seizures, varying from generalized spasms and tremors to generalized clonic activity with atonia and tail extension are seen. Cortical EEG reveals frequent spontaneous epileptic activity, including epileptiform discharges and seizures. Transgenic mice exhibit an approximately 20-fold increase in the number of interictal spikes. Overexpression results in aberrant myelin formation and axonal degeneration (at 12 months of age), and demyelination (by 24 months).
BAC clone RP23-460J18, carrying the full-length mouse Lmnb1 gene was isolated from a C57BL/6J-background Roswell Park Cancer Institute (RPCI) library. A 177.20 kb fragment encoding the entire locus was introduced to BAC vector pBACe3.6. The vector was subsequently microinjected into C57BL/6J fertilized oocytes. The resultant mice were maintained on a C57BL/6J background by the donating laboratory. This is founder line 1.
Expressed Gene | Lmnb1, lamin B1, mouse, laboratory |
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Site of Expression |
Allele Name | transgene insertion 1, Ying-Hui Fu |
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Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | Lmnb1BAC |
Gene Symbol and Name | Tg(Lmnb1)1Yfu, transgene insertion 1, Ying-Hui Fu |
Gene Synonym(s) | |
Promoter | Lmnb1, lamin B1, mouse, laboratory |
Expressed Gene | Lmnb1, lamin B1, mouse, laboratory |
Strain of Origin | C57BL/6J |
Chromosome | UN |
Molecular Note | The transgene contains BAC RP23-460J18. Lines 1 and 2 were generated with 4- and 2.5-fold increased expression, respectively. |
Hemizygotes are viable and fertile, but homozygotes are not.
When using the C57BL/6J-Tg(LMNB1)1Yfu/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #023083 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Hemizygous or Non Carrier for Tg(LMNB1)1Yfu |
Frozen Mouse Embryo | C57BL/6J-Tg(LMNB1)1Yfu/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C57BL/6J-Tg(LMNB1)1Yfu/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | C57BL/6J-Tg(LMNB1)1Yfu/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | C57BL/6J-Tg(LMNB1)1Yfu/J Frozen Embryo | $3373.50 |
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