Description

Strain Information

Type Chromosome Aberration; Deletion; Additional information on Mice with Chromosomal Aberrations. Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator James Lupski,   Baylor College of Medicine

Description
These mutant mice possess an engineered deletion spanning approximately 3 Mb on mouse Chromosome 11. The region involved encompasses a chromosomal segement that shares conserved synteny with the Smith-Magenis syndrome (SMS) critical interval on human Chromosome 17. Mice carrying one copy of the deletion prove to be viable while mice homozygous for the deletion are embryonic lethal. Heterozygous males suffer from reduced fertility, exhibiting reduced sperm counts and an increase in sperm structural abnormalities. Mutant mice weigh less than their wild type littermates at birth but rapidly gain weight such that by 4 months of age, they exceed wild type weight and eventually become obese (60 grams by 8 months of age). Mutant mice exhibit craniofacial abnormalities characterized by overall shorter skulls with broader, shorter snouts and nasal bones. Mutants also produce abnormal electroencephalograms (EEG) with tonic clonic-type seizures being observed in 22% of the mice tested. Behavioral studies involving heterozygous mice found that male mutants are hypoactive and display a shorter average circadian period than wildtype mice. This mutant mouse may be useful in studies exploring the consequences of deletions involving the SMS critical interval. (Mice bearing the reciprocal duplication are also available; see Stock: 005536)

Development
Chromosome-engineering cassettes were inserted into mouse chromosome 11 of 129S7/SvEvBrd-derived AB2.2 embryonic stem (ES) cells, bracketing a span of approximately 3 Mb between the Cops (proximal point) and Zfp179 (distal point) loci. The cassette placed at the distal locus contained most of the Zfp179 gene (excluding exon 16), a tyrosinase minigene, a 5' portion of an hprt minigene, a loxP site and neomycin resistance gene. The cassette placed at the proximal locus contained Cops exons III to VI, a puromycin resistance gene, a loxP site, a 3' portion of an hprt minigene and a Krt1-14-agouti transgene. Double-targeted ES cells were subjected to transient cre recombinase expression with subsequent selection of recombinants buy using HAT media. Correctly targeted ES cells were injected into C57BL/6-Tyr^c-Brd blastocysts and the resulting chimeric mice were mated to C57BL/6-Tyr^c-Brd mice for eight generations (4/2005) before being mated to C57BL/6J at The Jackson Laboratory.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Deletion

003374	B6;129S2-H2dlAb1-Ea/J
005654	B6C3-Del(16Cbr1-ORF9)1Rhr/J
002802	C3.BLiA Pde6b+-Krd/J
004406	C3HeB/FeJ-Pou3f4del-J/J
002142	STOCK 11R30m/J
004711	STOCK Ednrbs-52Pub

View Deletion     (6 strains)

Additional Web Information

Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Developmental Biology Research
Craniofacial and Palate Defects
Embryonic Lethality (Homozygous)

Reproductive Biology Research
Fertility Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Del(11Cops3-Zfp179)1Jrl
Allele Name		deletion, Chr 11, James R Lupski 1
Allele Type		Targeted (other)
Common Name(s)		Del(11Csn3-Zfp179)1Jrl; Del1Jrl; df(11)17;
Mutation Made By		Katherina Walz,   Baylor College of Medicine
Strain of Origin		129S7/SvEvBrd-Hprt1
ES Cell Line Name		AB2.2
ES Cell Line Strain		129S7/SvEvBrd-Hprt1
Molecular Note		A deletion between Csn3 and Zfp179 was engineered in ES cells by targeted insertion of complementary partial Hprt-loxP constructs at each site. Cre recombinase actived deleted the intervening region and reconstructed the Hprt minigene for selection purposes. [MGI Ref ID J:83302]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Walz K; Caratini-Rivera S; Bi W; Fonseca P; Mansouri DL; Lynch J; Vogel H; Noebels JL; Bradley A; Lupski JR. 2003. Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: phenotypic consequences of gene dosage imbalance. Mol Cell Biol 23(10):3646-55. [PubMed: 12724422]  [MGI Ref ID J:83302]

Additional References

Del(11Cops3-Zfp179)1Jrl related

Bi W; Yan J; Shi X; Yuva-Paylor LA; Antalffy BA; Goldman A; Yoo JW; Noebels JL; Armstrong DL; Paylor R; Lupski JR. 2007. Rai1 deficiency in mice causes learning impairment and motor dysfunction, whereas Rai1 heterozygous mice display minimal behavioral phenotypes. Hum Mol Genet 16(15):1802-13. [PubMed: 17517686]  [MGI Ref ID J:125089]

Walz K; Paylor R; Yan J; Bi W; Lupski JR. 2006. Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2). J Clin Invest 116(11):3035-41. [PubMed: 17024248]  [MGI Ref ID J:114996]

Walz K; Spencer C; Kaasik K; Lee CC; Lupski JR; Paylor R. 2004. Behavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2). Hum Mol Genet 13(4):367-78. [PubMed: 14709593]  [MGI Ref ID J:88027]

Yan J; Bi W; Lupski JR. 2007. Penetrance of craniofacial anomalies in mouse models of Smith-Magenis syndrome is modified by genomic sequence surrounding Rai1: not all null alleles are alike. Am J Hum Genet 80(3):518-25. [PubMed: 17273973]  [MGI Ref ID J:125240]

Yan J; Keener VW; Bi W; Walz K; Bradley A; Justice MJ; Lupski JR. 2004. Reduced penetrance of craniofacial anomalies as a function of deletion size and genetic background in a chromosome engineered partial mouse model for Smith-Magenis syndrome. Hum Mol Genet 13(21):2613-24. [PubMed: 15459175]  [MGI Ref ID J:94405]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as heterozygotes (mice carry only one copy of the deletion).
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.

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

Contact information

General inquiries

Contracts Administration

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

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.