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| 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. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Noncarrier x Hemizygote (Female x Male) 06-JUN-12 Mating System Hemizygote x Noncarrier (Female x Male) 06-JUN-12 Species laboratory mouse Donating Investigator Julie K. Andersen, Buck Institute for Age Research 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.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Gfap
017523 129S6.Cg-Tg(Gfap-TK)7.1Mvs/RhnJ 010670 B6.129S7-Gfaptm1Mes/J 010835 B6.Cg-Tg(Gfap-EGFP)3739Sart/J 005698 B6.Cg-Tg(Gfap-TK)7.1Mvs/J 012886 B6.Cg-Tg(Gfap-cre)73.12Mvs/J 012887 B6.Cg-Tg(Gfap-cre)77.6Mvs/J 002642 B6;129S-Gfaptm1Mes/J View Strains carrying other alleles of Gfap (7 strains)
Phenotype
Phenotype Information
assigned by genotype
Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan/0
involves: C57BL/6
- nervous system phenotype
- abnormal dopaminergic neuron morphology
- following induction of transgene expression surviving tyrosine hydroxylase positive cells in mesencephalic cultures prepared from E14 embryos show significant loss of neurite processes (MGI Ref ID J:132679)
- loss of dopaminergic neurons
- induction of transgene expression results in significant loss of tyrosine hydroxylase positive cells in mesencephalic cultures prepared from E14 embryos (MGI Ref ID J:132679)
- a 2 week induction period results in a 40% loss of dopaminergic neurons in the substantia nigra (MGI Ref ID J:132679)
- loss of dopaminergic neurons is prevented by deprenyl co-treatment (MGI Ref ID J:132679)
- removal of doxycycline from the feed does not reverse cell loss (MGI Ref ID J:132679)
- abnormal microglial cell activation
- following induction, local microglial activation in the substantia nigra and striatum but not in the cortex (MGI Ref ID J:132679)
- abnormal microglial cell morphology
- induction increases microglia numbers by about 17% (MGI Ref ID J:132679)
- abnormal neuron physiology
- following induction elevated levels of H2O2 are found in the media of cultures of mesencephalic cultures (MGI Ref ID J:132679)
- H2O2 levels are elevated in isolated ST dopaminergic synaptosomes following induction of transgene expression (MGI Ref ID J:132679)
- elevated levels of mitochondrial O2- levels in dopaminergic neurons following induction (MGI Ref ID J:132679)
- neurodegeneration
- irreversible dopaminergic substantia nigra neurodegeneration following induction of transgene expression (MGI Ref ID J:132679)
- behavior/neurological phenotype
- hypoactivity
- locomotor activity is reduced following 2 weeks of doxycycline treatment (MGI Ref ID J:132679)
- hematopoietic system phenotype
- abnormal microglial cell morphology
- induction increases microglia numbers by about 17% (MGI Ref ID J:132679)
- immune system phenotype
- abnormal microglial cell activation
- following induction, local microglial activation in the substantia nigra and striatum but not in the cortex (MGI Ref ID J:132679)
- abnormal microglial cell morphology
- induction increases microglia numbers by about 17% (MGI Ref ID J:132679)
This mouse can be used to support research in many areas including:
Neurobiology Research
Astrocyte Defects
astrocyte-specific marker
Behavioral and Learning Defects
Neurodegeneration
Parkinson's Disease
cell markers
Research Tools
Genetics Research
Tissue/Cell Markers: astrocytes
Neurobiology Research
astrocyte-specific marker
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan | ||
|---|---|---|---|
| Allele Name | transgene insertion 1, Julie K Andersen | ||
| Allele Type | Transgenic (random, expressed) | ||
| Mutation Made By | Julie Andersen, Buck Institute for Age Research | ||
| Strain of Origin | C57BL/6 | ||
| Expressed Gene | MAOB, monoamine oxidase B, human | ||
| Expressed Gene | lacZ, beta-galactosidase, E. coli | ||
| Expressed Gene | rtTA, reverse tetracycline-controlled transactivator, E. coli | ||
| The tetracycline repressor gene (Tetr), arose from chemically mutated Escherichia coli genome which was screened for tetracycline dependence (Gossen and Bujard, 1992). One mutant with a four amino acid residue change (rTetR) exhibited dependence on tetracycline for induction of the targeted gene and was used in the rtTA construct (Gossen et al, 1995). rTetr was fused at the C-terminus with the viral co-activator, virion protein 16 of the herpes simplex virus (VP-16). | |||
| Promoter | tetO, tet operator, | ||
| Promoter | Gfap, glial fibrillary acidic protein, mouse, laboratory | ||
| General Note | Phenotypic Similarity to Human Syndrome: Parkinson Disease (J:132679) | ||
| 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 expressionof 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. [MGI Ref ID J:132679] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan MCA,Separated MCA
Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Mallajosyula JK; Kaur D; Chinta SJ; Rajagopalan S; Rane A; Nicholls DG; Di Monte DA; Macarthur H; Andersen JK. 2008. MAO-B Elevation in Mouse Brain Astrocytes Results in Parkinson's Pathology. PLoS ONE 3(2):e1616. [PubMed: 18286173] [MGI Ref ID J:132679]
Additional References
Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan relatedLieu CA; Chinta SJ; Rane A; Andersen JK. 2013. Age-related behavioral phenotype of an astrocytic monoamine oxidase-B transgenic mouse model of Parkinson's disease. PLoS One 8(1):e54200. [PubMed: 23326597] [MGI Ref ID J:195707]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX18
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice can be bred as hemizygotes or homozygotes. Mating System Noncarrier x Hemizygote (Female x Male) 06-JUN-12 Hemizygote x Noncarrier (Female x Male) 06-JUN-12 Diet Information LabDiet® 5K20
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan
Price per Pair (US dollars $) Pair Genotype $296.00 Hemizygous for Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan x Noncarrier $296.00 Noncarrier x Hemizygous for Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan
Price per Pair (US dollars $) Pair Genotype $384.80 Hemizygous for Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan x Noncarrier $384.80 Noncarrier x Hemizygous for Tg(Gfap-rtTA,tetO-MAOB,-lacZ)1Jkan Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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