Overview

This strain harbors mutations in the Maob and Maob genes which abolish gene function. These mice exhibit increased reactivity to stress,increased aggression and may be useful for studying MAOA and MAOB-related behaviors and disorders.

Donating Investigator

Jean Shih, University of Southern California

Genetic overview

Genetic Background	Generation

Maoa^K284stop

Allele Type	Gene Symbol	Gene Name
Spontaneous	Maoa	monoamine oxidase A

Maob^tm1Shih

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Maob	monoamine oxidase B

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Research Applications

Neurobiology Research
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

This strain carries two mutant alleles, a knockout of the X-linked monoamine oxidase B (Maob) gene and a spontaneous mutation designated Maoa^K284stop in the monoamine oxidase A (Maoa) gene. The two mutations lie 24kb apart. MAO A/B deficient mice are viable, fertile, and normal in size. Maoa and Maob are mitochondrial enzymes which oxidize neurotransmitters and dietary amines. These mutants lack both MAOA and MAOB activity in the brain and liver resulting in increased levels of phenylethylamine, serotonin, dopamine, and norepinephrine. These mice exhibit increased reactivity to stress and increased aggression. These mice may be useful for studying MAOA and MAOB-related behaviors and disorders.

Development

A targeting vector was designed to replace exon 6 of the X-linked monoamine oxidase B (Maob) gene with a neomycin resistance (neo) cassette. The construct was electroporated into either 129S/SvEv-derived CCE embryonic stem (ES) cells or 129S4/SvJae-derived CCE ES cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to 129/Sv females. The male offspring were backcrossed at least 25 generations to 129/Sv females resulting in Maob deficient mice (Stock No. 014133). A mutation, designated Maoa^K284stop, arose spontaneously in exon 8 of the X-linked monoamine oxidase A (Maoa) gene of one male animal. This mutation was caused by a transversion at nucleotide 863, resulting in a premature stop codon at residue 284. This mutant male was backcrossed to a 129/Sv female, and the resulting female offspring were bred to 129/Sv males. Half of the resulting male offspring carried both mutations. Upon arrival at The Jackson Laboratory, mice were bred to 129S1/SvImJ (Stock No. 002448) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. 4 of the 27 markers throughout the genome suggested a C57BL/6 genetic contribution from an unknown source.

Control Suggestions

Approximate Controls

002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Chen K; Holschneider DP; Wu W; Rebrin I; Shih JC. 2004. A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior. J Biol Chem 279(38):39645-52PubMed: 15272015 MGI: J:93356

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Genetics

Maoa^K284stop

Allele Symbol: Maoa^K284stop

Allele Name	K284stop
Allele Type	Spontaneous
Allele Synonym(s)	MAO A KO; Maoa^A863T
Gene Symbol and Name	Maoa, monoamine oxidase A
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	X
Molecular Note	An A-to-T at coding nucleotide 850 in exon 8 created a stop codon at lysine codon 284 (p.K284*).
Mutations Made By	Jean Shih, University of Southern California

Maob^tm1Shih

Allele Symbol: Maob^tm1Shih

Allele Name	targeted mutation 1, Jean C Shih
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	MAOB KO
Gene Symbol and Name	Maob, monoamine oxidase B
Gene Synonym(s)
Strain of Origin	129S/Sv
Chromosome	X
General Note	ES cell line = CCE (129S/SvEv-Gpi1^c) or J1 (129S4/SvJae).
Molecular Note	The gene was disrupted by insertion of a neo cassette into exon 6 via homologous recombination resulting in a premature stop codon and protein truncation. Enzyme assays of brain and liver extracts from mutant mice demonstrated background levels of enzyme activity. Western blot and immunohistochemical analyses failed to detect protein product.
Mutations Made By	Jean Shih, University of Southern California

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Neurotransmitter Receptor and Synaptic Vesicle Defects
- Neurodegeneration
- Behavioral and Learning Defects
- Channel and Transporter Defects
Developmental Biology Research
- Internal/Organ Defects
  - brain

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Maoa^K284stop Maob^tm1Shih/Y
either: (involves: 129S/SvEv * 129S6/SvEvTac) or (involves: 129S4/SvJae * 129S6/SvEvTac)

behavior/neurological phenotype

decreased exploration in new environment
- exploratory activity is reduced as is time spent in the center of the field

increased aggression towards mice
- in the resident-intruder test mutants display a significant increase in anti-social behavior with a decrease in latency to attack and increased time spent chasing the intruder, as well as a decrease in investigative behavior

increased anxiety-related response
- in an elevated Plus-maze, mutants exhibit more freezing or crouching postures, fewer entries into either the open or closed arms, proportionally more entries into the closed arms, and fewer rearing events

homeostasis/metabolism phenotype

increased dopamine level
- dopamine levels are increased 1.7-fold

increased noradrenaline level
- brain levels of norepinephrine and phenylethylamine are increased 2.2-, and 15.7-fold, respectively

increased serotonin level
- brain levels of serotonin are increased 8.5-fold

nervous system phenotype

increased noradrenaline level
- brain levels of norepinephrine and phenylethylamine are increased 2.2-, and 15.7-fold, respectively

increased serotonin level
- brain levels of serotonin are increased 8.5-fold

References

Chen K; Holschneider DP; Wu W; Rebrin I; Shih JC. 2004. A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior. J Biol Chem 279(38):39645-52PubMed: 15272015 MGI: J:93356

Additional - Maoa^K284stop related

Additional - Maob^tm1Shih related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Pyrosequencing:Maoa
- Standard PCR:Maob
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, double homozygous females may be bred to double hemizygous males.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129S-Maoa^K284stop Maob^tm1Shih/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #014134 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	X linked -Heterozygous females and Non carrier males for Maoa<K284stop>, Heterozygous females and Non carrier males for Maob<tm1Shih>, 1 pair minimum

Related Products and Services

Frozen Mouse Embryo	B6;129S-Maoa<K284stop> Maob<tm1Shih>/J	$2595.00
Frozen Mouse Embryo	B6;129S-Maoa<K284stop> Maob<tm1Shih>/J	$2595.00
Frozen Mouse Embryo	B6;129S-Maoa<K284stop> Maob<tm1Shih>/J	$3373.50
Frozen Mouse Embryo	B6;129S-Maoa<K284stop> Maob<tm1Shih>/J	$3373.50

Payment Terms and Conditions

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

MaoaK284stop

Allele Symbol: MaoaK284stop

Maobtm1Shih

Allele Symbol: Maobtm1Shih

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: MaoaK284stop Maobtm1Shih/Yeither: (involves: 129S/SvEv * 129S6/SvEvTac) or (involves: 129S4/SvJae * 129S6/SvEvTac)

behavior/neurological phenotype

homeostasis/metabolism phenotype

nervous system phenotype

References

Additional - MaoaK284stop related

Additional - Maobtm1Shih related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Maoa^K284stop

Allele Symbol: Maoa^K284stop

Maob^tm1Shih

Allele Symbol: Maob^tm1Shih

Genotype: Maoa^K284stop Maob^tm1Shih/Y
either: (involves: 129S/SvEv * 129S6/SvEvTac) or (involves: 129S4/SvJae * 129S6/SvEvTac)

Additional - Maoa^K284stop related

Additional - Maob^tm1Shih related