C57BL/6-Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan/J

Stock number: 017955
Research areas: Neurobiology Research, Research Tools

Description

These transgenic mice allow inducible astroglia-specific expression of human MAOB (monoamine oxidase B) and lacZ (beta-galactosidase). With induction, they exhibit neurodegeneration, decreased locomotor activity, mitochondrial dysfunction, astrogliosis, and microglial activation. This strain may have applications in studies related to the initiation and progression of Parkinson's disease.

Detailed description

Monoamine oxidase B catalyzes dopamine oxidative de-amination predominantly in glial cells, producing large amounts of reactive oxygen species. Monoamine oxidase B inhibitors act to increase synaptic dopamine by blocking degradation and are used in treatment to delay the progression of symptoms of Parkinson's disease. These transgenic mice have inducible astroglia-specific expression of human MAOB (monoamine oxidase B) and lacZ (beta-galactosidase) under the control of the tetO, tetracycline-responsive regulatory element. Administration of doxycycline induces an approximately 2.5 fold increase in astrocyte-specific expression of MAOB. Transgene expression is detected only after induction in the brain by RT-PCR and specifically in astrocytes by immunohistochemical analysis. Induced elevated levels of MAOB result in progressive loss of dopaminergic neurons in the substantia nigra, a decrease in mitochondrial complex I activity and an increase in mitochondrial oxidative stress in dopaminergic neurons in the substantia nigra. Doxycycline treated transgenic mice exhibit astrogliosis, decreased locomotor activity and nigrostriatal microglial activation. The Donating Investigator reports that mice that are homozygous for the transgene are viable, and normal in size.

Development

A transgenic construct containing a human MAOB (monoamine oxidase B) cDNA and lacZ (beta-galactosidase) gene under the control of the tetO, tetracycline-responsive regulatory element, and a second transgenic construct containing rtTA (reverse tetracycline-controlled transactivator) under the control of the mouse Gfap (glial fibrillary acidic protein) promoter were co-injected into fertilized C57BL/6 mouse eggs. Founder animals were bred to C57BL/6, and maintained on the C57BL/6 background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan
Name: transgene insertion 1, Julie K Andersen
MGI accession ID: MGI:5014211
Generation method: Transgenic
Attributes: Reporter; Inducible; Inserted expressed sequence; Humanized sequence; Transactivator
Marker symbol: Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan
Marker name: transgene insertion 1, Julie K Andersen
Chromosome: UN
Strain of origin: C57BL/6
Expressed genes: rtTA,reverse tetracycline-controlled transactivator,E. coli; MAOB,monoamine oxidase B,human; lacZ,beta-galactosidase,E. coli
Molecular note: This transgene consists of 2 co-injected constructs. One encodes for a reverse tetracycline responsive transactivator with expression driven by a murine Gfap promoter. The second has a bidirectional tetracycline responsive promoter that drives expression of a lacZ reporter and a human MOAB cDNA. Several founders were generated and the line with the highest level of expression was used for analyses. Line 1 was generated.