Overview

Also Known As:AU4

These mice carry an R451C mutation in exon 7 of the Nlgn3 (neuroligin 3) gene. mRNA is detected by real-time PCR analysis of brain from homozygous animals. Mutant mice exhibit enhancements in inhibitory synaptic transmission as well as spacial learning and memory, but show deficits in social interaction. This mutant mouse strain may be useful in studies of the pathophysiology of autism. Exon 7 is additionally flanked by loxP sites. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical abnormalities.

Donating Investigator

Dr. Thomas C. Sudhof, Stanford University School of Medicine

Genetic overview

Genetic Background	Generation

Nlgn3^tm1Sud

Allele Type	Gene Symbol	Gene Name
Targeted (Humanized sequence)	Nlgn3	neuroligin 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

These mice carry an R451C mutation in exon 7 of the gene. mRNA is detected by real-time PCR analysis of brain from homozygous animals. Mutant mice exhibit enhancements in inhibitory synaptic transmission as well as spacial learning and memory, but show deficits in social interaction. This mutant mouse strain may be useful in studies of the pathophysiology of autism. Exon 7 is additionally flanked by loxP sites. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical abnormalities.

Development

Residue 451 of exon 7 (encoding arginine) was mutated to create a cysteine substitution (R451C). The same exon was flanked by loxP sites. A neomycin-resistant cassette flanked by frt sites was inserted in intron 7. 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. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for three to nine generations. The neomycin cassette was removed through crosses with a Flp strain (background not specified).

Control Suggestions

Wild-type from the colony

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Tabuchi K; Blundell J; Etherton MR; Hammer RE; Liu X; Powell CM; Sudhof TC. 2007. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318(5847):71-6PubMed: 17823315 MGI: J:125344

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Genetics

Nlgn3^tm1Sud

Allele Symbol: Nlgn3^tm1Sud

Allele Name	targeted mutation 1, Thomas C Sudhof
Allele Type	Targeted (Humanized sequence)
Allele Synonym(s)	NL3^R451C
Gene Symbol and Name	Nlgn3, neuroligin 3
Gene Synonym(s)
Promoter	Nlgn3, neuroligin 3, mouse, laboratory
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Chromosome	X
Molecular Note	Exon 7 was replaced with an exon 7 carrying an arginine to cysteine amino acid substitution at position 451 (R451C). A neo cassette used as a selectable marker was removed via flip-mediated recombination leaving a floxed exon 7 carrying the mutation. The R451C substitution in the extracellular esterase-homology domain that results in increased endoplasmic reticulum retention in humans with autism spectrum disorder. PCR was used to confirm the insertion. Western blot analysis reveal a decrease in protein expression to 10% of wild-type levels. Authors state that this mutation is likely to cause a gain-of-function mutation.
Mutations Made By	Dr. Thomas Sudhof, Stanford University School of Medicine

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

autism spectrum disorder

Research Areas By Phenotype

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

Research Tools
- Neurobiology Research
- Cre-lox System
  - loxP-flanked Sequences
Neurobiology Research
- Cre-lox System
  - loxP-flanked Sequences
- Behavioral and Learning 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: Nlgn3^tm1Sud/Y
involves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

increased stereotypic behavior
- mice exhibit an abnormal bias in the direction of rotation during locomotion
- mice perform similarly to wild-type littermates on the first trial of an accelerating rotarod, however in the last several trials, mice exhibit enhanced performance, with increased time on the rotarod before falling off compared to wild-type mice
- the time spent performing stereotypic movements is enhanced during spontaneous open-field activity
- mice show increased vigor of stereotypic movements, indicated by greater force variance during periods of low mobility

enhanced learning
- mice exhibit increased learning rate but similar initial coordination on the accelerating rotarod

hyperactivity
- mice show greater number of wall jumps
- mice are hyperactive during open-field tests, showing increased total distance traveled and increased number of ambulatory episodes, however, no changes in movement velocity or in crossings through the center of the open field are seen

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

Genotype: Nlgn3^tm1Sud/Y
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

abnormal spatial learning
- mice exhibit an increase in ability to find hidden platform in a Morris water maze and a decrease in training days
- after training, mice cross to the precise location of the hidden platform almost twice as often as wild-type mice
- spatial learning behavior in a Morris water maze is enhanced

abnormal social investigation
- response to a novel caged adult is decreased compared to in wild-type mice
- Normal - however, locomotor activity, motor coordination, exploration of novel objects, and anxiety-related behaviors are normal and mice are capable of learning social interaction behaviors following repeated exposure to the same mouse
- mice spend less time interacting with other mice compared to wild-type mice

nervous system phenotype

abnormal inhibitory postsynaptic currents
- IPSC in response to GABA puff is increased relative to in wild-type mice
- IPSC strength is increased by about 50% relative to in wild-type mice
- inhibitory postsynaptic currents (IPSCs) frequency is increased by 50% relative to in wild-type mice

References

Tabuchi K; Blundell J; Etherton MR; Hammer RE; Liu X; Powell CM; Sudhof TC. 2007. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318(5847):71-6PubMed: 17823315 MGI: J:125344

Additional - Nlgn3^tm1Sud related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Nlgn3
- Genotyping resources and troubleshooting
Breeding Considerations

This targeted mutation is located on the X chromosome. When maintaining a live distribution colony, heterozygous females may be bred with hemizygous males. In order to keep some of the mice ideally suited for use when deletion of the floxed-mutant exon 7 is planned, some of the colony may be maintained by breeding homozygous females to hemizygous males.
- Additional Breeding and Husbandry Support
Citation
When using the AU4 mouse strain in a publication, please cite the originating article(s) and include JAX stock #008475 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 Wild-type males for Nlgn3<tm1Sud>

Related Products and Services

Frozen Mouse Embryo	B6;129-Nlgn3<tm1Sud>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129-Nlgn3<tm1Sud>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6;129-Nlgn3<tm1Sud>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6;129-Nlgn3<tm1Sud>/J Frozen Embryo	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:AU4

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Nlgn3tm1Sud

Allele Symbol: Nlgn3tm1Sud

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Nlgn3tm1Sud/Yinvolves: 129S1/Sv * 129X1/SvJ

behavior/neurological phenotype

Genotype: Nlgn3tm1Sud/Yinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological phenotype

nervous system phenotype

References

Additional - Nlgn3tm1Sud 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

Nlgn3^tm1Sud

Allele Symbol: Nlgn3^tm1Sud

Genotype: Nlgn3^tm1Sud/Y
involves: 129S1/Sv * 129X1/SvJ

Genotype: Nlgn3^tm1Sud/Y
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Additional - Nlgn3^tm1Sud related