Overview

Sapap3^-/- (SAPAP3-null) mice exhibit characteristics of human obsessive compulsive disorder (excessive self-grooming, facial lesions, anxiety behavior and therapeutic response to fluoxetine) and altered cortico-striatal neurotransmission. These mice may be useful in studying OCD and other neuropsychiatric disease.

Donating Investigator

Guoping Feng, Massachusetts Institute of Technology

Genetic overview

Genetic Background	Generation

Dlgap3^tm1Gfng

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Dlgap3	DLG associated protein 3

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Research Applications

Research Tools
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Sapap3^- (SAPAP3-null) allele has a deletion of the exon containing the translation initiation codon. No full-length protein expression from the targeted allele is detected by western blot analysis of brain lysate and postsynaptic density fraction. Heterozygous mice (Sapap3^+/-) are viable and fertile with no reported abnormalities. Occasionally, heterozygotes older than ten months of age may have facial skin lesions. Homozygous mice (Sapap3^-/-) exhibit behavioral and neurological abnormalities. Specifically, Sapap3^-/- mice have characteristics of human obsessive compulsive disorder (excessive self-grooming, facial lesions and anxiety behavior) and altered cortico-striatal neurotransmission. The obsessive compulsive disorder behaviors of homozygous mice can be ameliorated by fluoxetine treatment. Homozygotes are fertile and breed when young and devoid of skin lesions. However, the donating investigator does not recommend maintaining the colony by breeding homozygous mice together: this would select mice for less severe phenotypes as they will breed better than the severe mice. The donating investigator also reports they have not observed Sapap3^-/- mice excessively grooming their cagemates.

Development

A targeting vector was designed designed by Dr. Guoping Feng (while at Duke University) to insert a neomycin cassette and delete exon 3 (containing the translation initiation codon) of the synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 locus (Dlgap3; Sapap3). The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric mice were bred with C57BL/6 mice to establish the mutant colony. The donating investigator reports that Sapap3^- mice were subsequently backcrossed to C57BL/6J mice for at least ten generations. During backcrossing, the Y chromosome was fixed to the C57BL/6J genetic background. In 2014, Dr. Feng (now at Massachusetts Institute of Technology) sent heterozygous mice to The Jackson Laboratory Repository. Upon arrival, males were used to cryopreserve sperm. To establish the living mouse colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J inbred females (Stock No. 000664).

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Welch JM; Lu J; Rodriguiz RM; Trotta NC; Peca J; Ding JD; Feliciano C; Chen M; Adams JP; Luo J; Dudek SM; Weinberg RJ; Calakos N; Wetsel WC; Feng G. 2007. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature 448(7156):894-900PubMed: 17713528 MGI: J:125181

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Genetics

Dlgap3^tm1Gfng

Allele Symbol: Dlgap3^tm1Gfng

Allele Name	targeted mutation 1, Guoping Feng
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Sapap3^-
Gene Symbol and Name	Dlgap3, DLG associated protein 3
Gene Synonym(s)
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	4
Molecular Note	Exon 3 containing the translation initiation codon was replaced with a neo cassette. The absence of protein product was confirmed by western blot analysis of brain lysate and postsynaptic density fraction.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Neurobiology Research
Neurobiology Research
- Cerebellar Defects
- Behavioral and Learning Defects
  - high anxiety
- Neurotransmitter Receptor and Synaptic Vesicle Defects
- Cortical Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Dlgap3^tm1Gfng/Dlgap3^tm1Gfng
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

abnormal sleep pattern
- Normal - however, treatment with fluoxetine for 6 days reduces the number of sleeping bouts and increases the sleeping time per bout
- mice have increased sleeping bouts but the time slept per bout was reduced relative to in wild-type mice
- mice sleep less during normal sleeping periods and sleep ore during active times compared to wild-type mice

enhanced behavioral response to xenobiotic
- grooming behavior and anxiety-related behaviors are reduced following treatment with fluoxetine for 6 days whereas grooming behavior in similarly treated wild-type mice is unchanged
- however, a single treatment of fluoxetine has no effect on grooming behavior
- treatment with fluoxetine for 6 days reduced the number of sleeping bouts and increased the sleeping time per bout

increased anxiety-related response
- Normal - however, activity levels overall are normal and treatment with fluoxetine for 6 days reduces anxiety-related behaviors in a dark-light test without affecting total activity levels
- in a dark-light test, mice take more time to cross from the dark to the lit chamber and spent less time in the lit chamber compared to wild-type mice
- in an elevated zero maze test, mice take longer to cross into the open areas and spent less time exploring than do wild-type mice

increased grooming behavior
- Normal - however, grooming behavior is reduced following treatment with fluoxetine for 6 days whereas grooming behavior in similarly treated wild-type mice is unchanged
- mice exhibit increased grooming bouts and spend more time self-grooming prior to lesion formation than do wild-type mice

increased thigmotaxis
- Normal - however, activities along the walls and in corners is normal
- in an open field test mice spend more time long walls and spend less time exploring than do wild-type mice

integument phenotype

skin lesions
- by 4 to 6 months, all mice develop lesions on their heads, neck and snout regions
- Normal - however, pre-lesion mouse skin is normal
- lesions begin as hairless skin under eyes, or swelling of the snout and progress to relatively symmetrical bilateral lesions encompassing large parts of the head and neck
- skin with lesions contains increased lymphocytic/granulocytic infiltrate

nervous system phenotype

abnormal excitatory postsynaptic potential
- field excitatory postsynaptic potential (fEPSP) in the presence of picrotoxin is decreased compared to in wild-type mice
- Normal - however, axon excitability and presynaptic function are normal as is CA3-CA1 hippocampal basal synaptic transmission
- NMDAR-dependent fEPSP amplitudes are increased relative to in wild-type mice

abnormal striatum morphology
- the thickness of the dense layer, but not the light layer, in postsynaptic densities of cortico-striatal synapses is reduced compared to in wild-type mice

enhanced NMDA-mediated synaptic currents
- Normal - however, CA3-CA1 hippocampal basal synaptic transmission is normal
- NMDAR-dependent fEPSP amplitudes are increased relative to in wild-type mice

References

Welch JM; Lu J; Rodriguiz RM; Trotta NC; Peca J; Ding JD; Feliciano C; Chen M; Adams JP; Luo J; Dudek SM; Weinberg RJ; Calakos N; Wetsel WC; Feng G. 2007. Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice. Nature 448(7156):894-900PubMed: 17713528 MGI: J:125181

Additional - Dlgap3^tm1Gfng related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Dlgap3-Alternate 2
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony, or to C57BL/6J inbred mice (Stock No. 000664). Homozygous mice exhibit characteristics of human obsessive compulsive disorder (excessive self-grooming and facial lesions). Homozygotes are fertile and breed when young and devoid of skin lesions. However, the donating investigator does not recommend maintaining the colony by breeding homozygous mice together: this would select mice for less severe phenotypes as they will breed better than the severe mice. The donating investigator also reports they have not observed homozygotes excessively grooming their cagemates.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129-Dlgap3^tm1Gfng/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008733 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
	Heterozygous or Wildtype for Dlgap3<tm1Gfng>

Related Products and Services

Frozen Mouse Embryo	B6.129-Dlgap3<tm1Gfng>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Dlgap3<tm1Gfng>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129-Dlgap3<tm1Gfng>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129-Dlgap3<tm1Gfng>/J Frozen Embryo	$3373.50

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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.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Dlgap3tm1Gfng

Allele Symbol: Dlgap3tm1Gfng

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Dlgap3tm1Gfng/Dlgap3tm1Gfnginvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

integument phenotype

nervous system phenotype

References

Additional - Dlgap3tm1Gfng 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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Dlgap3^tm1Gfng

Allele Symbol: Dlgap3^tm1Gfng

Genotype: Dlgap3^tm1Gfng/Dlgap3^tm1Gfng
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Dlgap3^tm1Gfng related