Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation +pN1 Generation Definitions   Donating Investigator Jean Shih,   University of Southern California

Description
These MAO-A^neo mutant mice possess a single loxP site downstream of exon 11, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 12 of the X-linked monoamine oxidase A (Maoa) gene. Hemizygous males and homozygous females are viable, fertile, and normal in size. MAO-A is a mitochondrial enzyme that oxidizes monoamine neurotransmitters and dietary monoamines. Insertion of the floxed-neo cassette results in a truncation of the C-terminal of MAO-A resulting in expression of a hypomorphic MAO-A transcript in the prefrontal cortex and amygdala. These mice exhibit an increase of pyramidal neuron dendritic length in the orbitofrontal cortex, a reduction in basilar dendritic length, and an increase in apical dendritic length. These mice display reduction in social interaction, reduction in anxiety like behaviors, and reduction in total locomotor activity.

When these mutant mice are bred to mice that express Cre recombinase, resulting offspring may contain multiple gene rearrangments in cre-expressing tissues. Offspring will contain either intact floxed-exon 12 (MAO-A^flox), intact floxed-neo cassette, or excision of both exon 12 and the neo cassette (MAO-A^Δ12 KO). MAO-A^flox mice exhibit MAO-A catalytic activity similar to wildtype littermates. MAO-A^Δ12 KO mice lack MAO-A activity in the brain. These mice may be useful for studying MAO-A-related aggression and abnormal development of neural circuits under excess serotonin.

Development
A targeting vector was designed to insert a single loxP site downstream of exon 11, and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 12 of the X-linked monoamine oxidase A (Maoa) gene. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. Resulting chimeric males were bred with 129S6/SvEvTac females and their offspring were backcrossed to 129S6/SvEvTac mice to establish a colony of MAO-A^neo. Upon arrival, mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation.

Control Information

	Control
	Heterozygote from the colony
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Maoa

018589	129-MaoaK284stop/J
014134	B6;129S-MaoaK284stop Maobtm1Shih/J
014132	C3H/HeOuJ-MaoaTg(H2-K1-Ifnb1)8Seif/J

View Strains carrying other alleles of Maoa     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Brunner Syndrome   (MAOA) Monoamine Oxidase A; MAOA   (MAOA)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Maoa^tm1Shih/Maoa^tm1Shih

        involves: 129S4/SvJae

• cardiovascular system phenotype
• abnormal myocardial fiber physiology
  • myocytes treated with norepinephrine exhibit reduced reactive oxygen species formation compared with similarly treated wild-type mice   (MGI Ref ID J:170067)
• decreased left ventricle systolic pressure
  • before and after transverse aortic constriction   (MGI Ref ID J:170067)
• decreased response of heart to induced stress
  • at 9 weeks after transverse aortic constriction, mice exhibit improved left ventricular function, no chamber dilation, and reduced levels of fibrosis compared with wild-type mice   (MGI Ref ID J:170067)
• homeostasis/metabolism phenotype
• decreased response of heart to induced stress
  • at 9 weeks after transverse aortic constriction, mice exhibit improved left ventricular function, no chamber dilation, and reduced levels of fibrosis compared with wild-type mice   (MGI Ref ID J:170067)

View Research Applications

Research Applications

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

Developmental Biology Research
Internal/Organ Defects

Neurobiology Research
Behavioral and Learning Defects
Channel and Transporter Defects
Cre-lox System
      loxP-flanked Sequences
Neurodegeneration
Neurotransmitter Receptor and Synaptic Vesicle Defects

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Maoatm1Shih
Allele Name		targeted mutation 1, Jean C Shih
Allele Type		Targeted (knock-out)
Common Name(s)		MAO-Aneo;
Mutation Made By		Jean Shih,   University of Southern California
Strain of Origin		129S4/SvJae
Gene Symbol and Name		Maoa, monoamine oxidase A
Chromosome		X
Gene Common Name(s)		1110061B18Rik; AA407771; MAO-A; MGC:27811; Mao; RIKEN cDNA 1110061B18 gene; expressed sequence AA407771;
Molecular Note		A loxP site was inserted upstream of exon 12. A floxed neo cassette was inserted downstream of exon 12. No enzymatic activity was detected. Removal of the neo cassette is required to restore enzymatic activity. [MGI Ref ID J:170067] [MGI Ref ID J:193013]

Genotyping

Genotyping Information

Genotyping Protocols

Maoa^tm1Shih, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Kaludercic N; Takimoto E; Nagayama T; Feng N; Lai EW; Bedja D; Chen K; Gabrielson KL; Blakely RD; Shih JC; Pacak K; Kass DA; Di Lisa F; Paolocci N. 2010. Monoamine oxidase A-mediated enhanced catabolism of norepinephrine contributes to adverse remodeling and pump failure in hearts with pressure overload. Circ Res 106(1):193-202. [PubMed: 19910579]  [MGI Ref ID J:170067]

Additional References

Maoa^tm1Shih related

Alzghoul L; Bortolato M; Delis F; Thanos PK; Darling RD; Godar SC; Zhang J; Grant S; Wang GJ; Simpson KL; Chen K; Volkow ND; Lin RC; Shih JC. 2012. Altered cerebellar organization and function in monoamine oxidase A hypomorphic mice. Neuropharmacology 63(7):1208-17. [PubMed: 22971542]  [MGI Ref ID J:192761]

Bortolato M; Chen K; Godar SC; Chen G; Wu W; Rebrin I; Farrell MR; Scott AL; Wellman CL; Shih JC. 2011. Social deficits and perseverative behaviors, but not overt aggression, in MAO-A hypomorphic mice. Neuropsychopharmacology 36(13):2674-88. [PubMed: 21832987]  [MGI Ref ID J:193013]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous females may be bred to hemizygous males.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Heterozygote from the colony
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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