Overview

Also Known As:16p11^flx, 16p11.2^flx

A copy number variation on human chromosome 16p11.2 is among the most common genetic variations found in autism spectrum disorders. 16p11^flx mice are a Cre or FLP recombinase-inducible mouse model of 16p11.2 deletion that has several loxP and frt sites flanking the corresponding 440 kbp region on mouse chromosome 7F3. These mice may be useful in studying basal ganglia circuitry and the pathophysiology of autism.

Donating Investigator

Ricardo E Dolmetsch, Stanford University

Genetic overview

Genetic Background	Generation

Igs14^tm1Dolm

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), Reporter, No functional change)	Igs14	intergenic site 14

Igs13^tm1Dolm

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Igs13	intergenic site 13

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Research Applications

Research Tools
Neurobiology Research
Sensorineural Research
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

A copy number variation (CNV) on human chromosome 16p11.2 is among the most common genetic variations found in autism spectrum disorders (ASD). Patients with this deletion display motor deficits, speech/language delay, and cognitive impairments, accompanied by ASD, attention deficit hyperactivity disorder (ADHD), seizures, and hearing disorders. Conversely, a duplication of 16p11.2 is associated with schizophrenia. The chromosome 16p11.2 CNV encompasses 26 genes that are highly conserved on mouse chromosome 7F3.

16p11^flx is a Cre or FLP recombinase-inducible mouse model of 16p11.2 deletion that has several loxP and frt sites flanking the 440 kbp region on mouse chromosome 7F3. Homozygous mice (16p11^flx) are viable and fertile with no reported gross physical or behavioral abnormalities.

Following Cre or FLP-mediated deletion of the entire region, a membrane-targeted fluorescent reporter gene (mCherry) is expressed. The donating investigator reports that for imaging large-scale anatomical structures, such as white matter tracts, mCherry fluorescence is very strong. For identification of single neuronal cell-bodies, however, immunohistochemical fluorescence might improve the outcome.

Mice with deletion of the genomic segment (16p11^-) are available at The Jackson Laboratory as Stock No. 025100.

The 16p11^flx model was created using two independent targeting events. Although the loxP/frt region near Coro1a is in relatively close proximity (440 kbp) to the loxP/frt region near Spn, the two loci have a small chance of segregating independently of one another. The donating investigator reports they never observed any crossing over between the two loci and they always segregated together.

Additionally, breeding heterozygous mice together at The Jackson Laboratory results in mice that are black, light chinchilla or albino. This suggests the 16p11^flx mice we received retained mESC-derived allele(s) at the tyrosinase locus (e.g., Tyr^c and/or Tyr^c-ch) that, because it is only ~40 kbp proximal on chromosome 7, appears to be segregating along with the 16p11^flx region. Depending upon future segregation patterns, available mice may be black, light chinchilla or albino.

Development

16p11^flx has several loxP and frt sites flanking the 440 kbp region on mouse chromosome 7F3; a region highly conserved with the human chromosome 16p11.2 region whose copy number variations are associated with autism spectrum disorders and schizophrenia.

Drs. Ricardo E. Dolmetsch and Thomas Portmann (while at Stanford University) created the two targeting vectors used to generate these 16p11^flx mice. The first vector was designed to insert a CMV-IE enhancer/chicken beta-actin/rabbit beta-globin hybrid promoter (from pCAGGS), loxP-frt-neomycin resistance cassette-loxP-frt-loxP sequence and polyA signal at the centromeric end of the coronin actin binding protein 1A locus (Coro1a). The insertion site was 1165 bp centromeric (transcriptionally downstream) of the last Coro1a exon to avoid disrupting endogenous expression prior to Cre recombination. The second targeting vector was designed to insert a translational stop codon (for all frames), loxP-frt-puromycin resistance cassette-loxP-frt sequence, rabbit b-globin intron, coding sequence mCherry fluorescent protein (with palmitoylation signal for membrane targeting) and polyA signal at the telomeric end of the sialophorin locus (Spn). The insertion site was 3336 bp telomeric (transcriptionally upstream) of the Spn gene to avoid disrupting endogenous expression prior to Cre recombination. Sequential targeting into 129 mouse embryonic stem cells (mESC [see note below]) resulted in mESC clones with cis arrangement (targeting into the same chromosome 7 homolog) or trans arrangement (each vector targeted into different chromosome 7 homologs). The modified mESCs were injected into blastocysts, implanted into pseudopregnant female mice, and chimeric males were subsequently bred to C57BL/6NCrl females and/or HPRT-Cre females (Hprt^tm1(cre)Mnn on a C57BL/6;CD1 mixed genetic background; see Stock No. 004302). Germline transmission was successful only for the cis arrangement, and animals with no recombination resulted in heterozygous floxed mice (16p11^flx/+). The 16p11^flx colony was bred to C57BL/6NCrl for at least five generations prior to sending black males to The Jackson Laboratory in 2014. Upon arrival, sperm was cryopreserved. To establish our living colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (from Stock No. 005304).

Additionally, breeding heterozygous mice together at The Jackson Laboratory results in mice that are black, light chinchilla or albino. While the Portmann et al. 2014 Cell Rep 7(4):1077-92 publication describes the mESC used were 129/OLA, the donating laboratory indicates it may have been a different 129 origin. Taken together, these data suggest the 16p11^flx mice we received retained mESC-derived allele(s) at the tyrosinase locus (e.g., Tyr^c and/or Tyr^c-ch) that, because it is only ~40 kbp proximal on chromosome 7, appears to be segregating along with the 16p11^flx region. Depending upon future segregation patterns, available mice may be black, light chinchilla or albino.

In 2015, a 32 SNP panel analysis (27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains), was performed on the first generation rederived live colony at The Jackson Laboratory Repository. This revealed one animal with 2 of 27 markers, one each on chromosomes 2 and 12, that were not fixed for C57BL/6 allele-type (e.g., still segregating for 129 allele-type markers). All 5 markers that determine C57BL/6 substrains were found to be C57BL/6N allele-type.

Expression Data

Expressed Gene	RFP, Red Fluorescent Protein, coral
Site of Expression	Following Cre or FLP-mediated deletion of the 440 kbp region on mouse chromosome 7F3region, a membrane-targeted fluorescent reporter gene (mCherry) is expressed in Cre or FLP expressing tissues.
Site of Expression	Following Cre or FLP-mediated deletion of the 440 kbp region on mouse chromosome 7F3region, a membrane-targeted fluorescent reporter gene (mCherry) is expressed in Cre or FLP expressing tissues.

Control Suggestions

Approximate Controls

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Portmann T; Yang M; Mao R; Panagiotakos G; Ellegood J; Dolen G; Bader PL; Grueter BA; Goold C; Fisher E; Clifford K; Rengarajan P; Kalikhman D; Loureiro D; Saw NL; Zhengqui Z; Miller MA; Lerch JP; Henkelman RM; Shamloo M; Malenka RC; Crawley JN; Dolmetsch RE. 2014. Behavioral abnormalities and circuit defects in the Basal Ganglia of a mouse model of 16p11.2 deletion syndrome. Cell Rep 7(4):1077-92PubMed: 24794428 MGI: J:210018

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Genetics

Igs14^tm1Dolm

Allele Symbol: Igs14^tm1Dolm

Allele Name	targeted mutation 1, Ricardo Dolmetsch
Allele Type	Targeted (Conditional ready (e.g. floxed), Reporter, No functional change)
Allele Synonym(s)
Gene Symbol and Name	Igs14, intergenic site 14
Gene Synonym(s)
Expressed Gene	RFP, Red Fluorescent Protein, coral
Site of Expression	Following Cre or FLP-mediated deletion of the 440 kbp region on mouse chromosome 7F3region, a membrane-targeted fluorescent reporter gene (mCherry) is expressed in Cre or FLP expressing tissues.
Strain of Origin	129P2/OlaHsd
Chromosome	7
Molecular Note	The targeting vector is designed to insert a translational stop codon (for all frames), loxP-frt-puromycin resistance cassette-loxP-frt sequence, rabbit b-globin intron, coding sequence mCherry fluorescent protein (with palmitoylation signal for membrane targeting) and polyA signal at the telomeric end of the sialophorin locus (Spn) gene. The insertion site is 3336 bp telomeric (transcriptionally upstream).

Igs13^tm1Dolm

Allele Symbol: Igs13^tm1Dolm

Allele Name	targeted mutation 1, Ricardo Dolmetsch
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)
Gene Symbol and Name	Igs13, intergenic site 13
Gene Synonym(s)
Site of Expression	Following Cre or FLP-mediated deletion of the 440 kbp region on mouse chromosome 7F3region, a membrane-targeted fluorescent reporter gene (mCherry) is expressed in Cre or FLP expressing tissues.
Strain of Origin	129P2/OlaHsd
Chromosome	7
Molecular Note	The targeting vector is designed to insert a CMV-IE enhancer/chicken beta-actin/rabbit beta-globin hybrid promoter (from pCAGGS), loxP-frt-neomycin resistance cassette-loxP-frt-loxP sequence and polyA signal at the centromeric end of the coronin actin binding protein 1A locus (Coro1a) gene. The insertion site is 1165 bp centromeric (transcriptionally downstream) of the last exon.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Genetics Research
  - Mutagenesis and Transgenesis: Cre-lox System
  - Tissue/Cell Markers: Cre-lox System
- Fluorescent Proteins
- Cre-lox System
  - loxP-flanked Sequences
  - loxP-flanked Sequences: Test/Reporter
- Developmental Biology Research
  - Cre-lox System
Neurobiology Research
- Fluorescent protein expression in neural tissue
- Neurodevelopmental Defects
  - Autism
- Cortical Defects
- Behavioral and Learning Defects
- Cre-lox System
  - loxP-flanked Sequences
  - loxP-flanked Sequences: Test/Reporter
- Ataxia (Movement) Defects
- Hearing Defects
Sensorineural Research
- Hearing Defects
Developmental Biology Research
- Neurodevelopmental 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: Igs13^tm1Dolm/Igs13⁺ Igs14^tm1Dolm/Igs14⁺
involves: 129P2/OlaHsd * C57BL/6N

normal phenotype

no abnormal phenotype detected
- mice were used to generate Del(7Coro1a-Spn)1Dolm

References

Portmann T; Yang M; Mao R; Panagiotakos G; Ellegood J; Dolen G; Bader PL; Grueter BA; Goold C; Fisher E; Clifford K; Rengarajan P; Kalikhman D; Loureiro D; Saw NL; Zhengqui Z; Miller MA; Lerch JP; Henkelman RM; Shamloo M; Malenka RC; Crawley JN; Dolmetsch RE. 2014. Behavioral abnormalities and circuit defects in the Basal Ganglia of a mouse model of 16p11.2 deletion syndrome. Cell Rep 7(4):1077-92PubMed: 24794428 MGI: J:210018

Additional - Igs13^tm1Dolm related

Additional - Igs14^tm1Dolm related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- End Point Analysis:Tyr alternative 1
- QPCR:Generic Neo Quantitative PCR-QPCR- 1.2
- Standard PCR:Igs13
- Standard PCR:Igs14-Alternate 2
- Standard PCR:Igs13-Alternate 1
- Standard PCR:Del(7Coro1a-Spn)Dolm-alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, mice homozygous for each targeted allele may be bred together.
Additionally, breeding heterozygous mice together at The Jackson Laboratory results in mice that are black, light chinchilla or albino. While the Portmann et al. 2014 Cell Rep 7(4):1077-92 publication describes the mESC used were 129/OLA, the donating laboratory indicates it may have been a different 129 origin. Taken together, these data suggest the 16p11^flx mice we received retained mESC-derived allele(s) at the tyrosinase locus (e.g., Tyr^c and/or Tyr^c-ch) that, because it is only ~40 kbp proximal on chromosome 7, appears to be segregating along with the 16p11^flx region. Depending upon future segregation patterns, available mice may be black, light chinchilla or albino.
- Additional Breeding and Husbandry Support
Citation
When using the 16p11.2^flx mouse strain in a publication, please cite the originating article(s) and include JAX stock #025330 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 Igs13<tm1Dolm> and for Igs14<tm1Dolm>

Related Products and Services

Frozen Mouse Embryo	B6N.129P2(Cg)-Igs13<tm1Dolm> Igs14<tm1Dolm>/J	$2595.00
Frozen Mouse Embryo	B6N.129P2(Cg)-Igs13<tm1Dolm> Igs14<tm1Dolm>/J	$2595.00
Frozen Mouse Embryo	B6N.129P2(Cg)-Igs13<tm1Dolm> Igs14<tm1Dolm>/J	$3373.50
Frozen Mouse Embryo	B6N.129P2(Cg)-Igs13<tm1Dolm> Igs14<tm1Dolm>/J	$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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Also Known As:16p11flx, 16p11.2flx

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Igs14tm1Dolm

Allele Symbol: Igs14tm1Dolm

Igs13tm1Dolm

Allele Symbol: Igs13tm1Dolm

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Igs13tm1Dolm/Igs13+ Igs14tm1Dolm/Igs14+involves: 129P2/OlaHsd * C57BL/6N

normal phenotype

References

Additional - Igs13tm1Dolm related

Additional - Igs14tm1Dolm 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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As:16p11^flx, 16p11.2^flx

Igs14^tm1Dolm

Allele Symbol: Igs14^tm1Dolm

Igs13^tm1Dolm

Allele Symbol: Igs13^tm1Dolm

Genotype: Igs13^tm1Dolm/Igs13⁺ Igs14^tm1Dolm/Igs14⁺
involves: 129P2/OlaHsd * C57BL/6N

Additional - Igs13^tm1Dolm related

Additional - Igs14^tm1Dolm related