JAX Mouse Strain Datasheet - 008475

B6;129-Nlgn3^tm1Sud/J

Stock No:: 008475

Targeted Mutation

Cryo Recovery

Overview

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

Neurobiology Research
Research Tools

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Base Price

Starting at:

$2,595.00 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):71-6. PubMed: 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)	A230085M13Rik; A230085M13Rik; HNL3; NL3; RIKEN cDNA A230085M13 gene
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

Research Areas By Genotype

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

Neurobiology Research
- Behavioral and Learning Defects
- Cre-lox System
  - loxP-flanked Sequences
Research Tools
- Cre-lox System
  - loxP-flanked Sequences
- Neurobiology Research

Mammalian Phenotype Terms by Genotype

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

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

behavior/neurological phenotype

abnormal social investigation
- 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
- response to a novel caged adult is decreased compared to in wild-type mice

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

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

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

hyperactivity
- 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
- mice show greater number of wall jumps

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
- mice show increased vigor of stereotypic movements, indicated by greater force variance during periods of low mobility
- the time spent performing stereotypic movements is enhanced during spontaneous open-field activity

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):71-6. PubMed: 17823315 MGI: J:125344

Additional - Nlgn3^tm1Sud related

Cellot G; Cherubini E. 2014. Reduced inhibitory gate in the barrel cortex of Neuroligin3R451C knock-in mice, an animal model of autism spectrum disorders. Physiol Rep 2(7):. PubMed: 25347860 MGI: J:228854
Chanda S; Marro S; Wernig M; Sudhof TC. 2013. Neurons generated by direct conversion of fibroblasts reproduce synaptic phenotype caused by autism-associated neuroligin-3 mutation. Proc Natl Acad Sci U S A 110(41):16622-7. PubMed: 24046374 MGI: J:202326
Etherton M; Foldy C; Sharma M; Tabuchi K; Liu X; Shamloo M; Malenka RC; Sudhof TC. 2011. Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function. Proc Natl Acad Sci U S A 108(33):13764-9. PubMed: 21808020 MGI: J:175606
Foldy C; Malenka RC; Sudhof TC. 2013. Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling. Neuron 78(3):498-509. PubMed: 23583622 MGI: J:197899
Hill-Yardin EL; Argyropoulos A; Hosie S; Rind G; Anderson P; Hannan AJ; O'Brien TJ. 2015. Reduced susceptibility to induced seizures in the Neuroligin-3(R451C) mouse model of autism. Neurosci Lett 589:57-61. PubMed: 25592157 MGI: J:219730
Karvat G; Kimchi T. 2012. Systematic autistic-like behavioral phenotyping of 4 mouse strains using a novel wheel-running assay. Behav Brain Res 233(2):405-14. PubMed: 22633921 MGI: J:190481
Kumar M; Duda JT; Hwang WT; Kenworthy C; Ittyerah R; Pickup S; Brodkin ES; Gee JC; Abel T; Poptani H. 2014. High resolution magnetic resonance imaging for characterization of the neuroligin-3 knock-in mouse model associated with autism spectrum disorder. PLoS One 9(10):e109872. PubMed: 25299583 MGI: J:223567
Rothwell PE; Fuccillo MV; Maxeiner S; Hayton SJ; Gokce O; Lim BK; Fowler SC; Malenka RC; Sudhof TC. 2014. Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors. Cell 158(1):198-212. PubMed: 24995986 MGI: J:214636

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	X linked Heterozygous females and Wild-type males for Nlgn3<tm1Sud>

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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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.

Terms Of Use

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

Nlgn3tm1Sud

Allele Symbol: Nlgn3tm1Sud

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

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

nervous system phenotype

behavior/neurological phenotype

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

behavior/neurological 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

Progeny testing is not required

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

Nlgn3^tm1Sud

Allele Symbol: Nlgn3^tm1Sud

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

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

Additional - Nlgn3^tm1Sud related