Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System See Colony Maintenance under the Health & husbandry tab         (Female x Male)   13-FEB-09 Species laboratory mouse Generation N4+F5 (14-MAR-11) Generation Definitions   Donating Investigator Thomas Sudhof,   Stanford University School of Medicine

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 Information

	Control
	Wild-type from the colony
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Nlgn3

008394	B6;129-Nlgn3tm2.1Sud/J
015835	STOCK Nlgn3tm2Sud/J

View Strains carrying other alleles of Nlgn3     (2 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Nlgn3^tm1Sud/Y

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• nervous system phenotype
• abnormal inhibitory postsynaptic currents
  • inhibitory postsynaptic currents (IPSCs) frequency is increased by 50% relative to in wild-type mice   (MGI Ref ID J:125344)
  • IPSC in response to GABA puff is increased relative to in wild-type mice   (MGI Ref ID J:125344)
  • IPSC strength is increased by about 50% relative to in wild-type mice   (MGI Ref ID J:125344)
• behavior/neurological phenotype
• abnormal social investigation
  • response to a novel caged adult is decreased compared to in wild-type mice   (MGI Ref ID J:125344)
  • mice spend less time interacting with other mice compared to wild-type mice   (MGI Ref ID J:125344)
  • 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   (MGI Ref ID J:125344)
• abnormal spatial learning
  • spatial learning behavior in a Morris water maze is enhanced   (MGI Ref ID J:125344)
  • mice exhibit an increase in ability to find hidden platform in a Morris water maze and a decrease in training days   (MGI Ref ID J:125344)
  • after training, mice cross to the precise location of the hidden platform almost twice as often as wild-type mice   (MGI Ref ID J:125344)

View Research Applications

Research Applications

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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Nlgn3tm1Sud
Allele Name		targeted mutation 1, Thomas Sudhof
Allele Type		Targeted (knock-in)
Common Name(s)		NL3R451C;
Mutation Made By		Thomas Sudhof,   Stanford University School of Medicine
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Nlgn3, neuroligin 3
Chromosome		X
Gene Common Name(s)		A230085M13Rik; HNL3; NL3; RIKEN cDNA A230085M13 gene;
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. [MGI Ref ID J:125344]

Genotyping

Genotyping Information

Genotyping Protocols

Nlgn3^tm1Sud, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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 Ref ID J:125344]

Additional References

Nlgn3^tm1Sud related

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 Ref ID J:175606]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	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.
Mating System	See Colony Maintenance under the Health & husbandry tab         (Female x Male)   13-FEB-09
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
- Use of MICE by companies or for-profit entities requires a license.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.