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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Dr. Thomas C. 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
015834	STOCK Nlgn3tm3.1Sud/J

View Strains carrying other alleles of Nlgn3     (3 strains)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Autism, Susceptibility to, X-Linked 1; AUTSX1

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Asperger Syndrome, X-Linked, Susceptibility to, 1; ASPGX1   (NLGN3) Autism   (NLGN3)

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		Dr. 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<+>
Promoter		Nlgn3, neuroligin 3, mouse, laboratory
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, Fast MCA

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]

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 Ref ID J:190481]

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	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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

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.

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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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