Description

Strain Information

Former Names B6C3.129S6-Del(16Cbr1-ORF9)1Rhr/J    (Changed: 19-JAN-06 ) Type Deletion; Additional information on Mice with Chromosomal Aberrations. Type Mutant Stock; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Roger Reeves,   Johns Hopkins Univ. Schl. Med

Description
These mice are monosomic for the mouse chromosome segment MMU16. The deleted segment contains mouse orthologs of 33 conserved and minimally conserved genes in the human Down's syndrome critical region (DSCR). The borders of the deletion are defined by the carbonyl reductase 1 (Cbr1) gene and a site adjacent to the myxovirus (influenza virus) resistance 2 (Mx2) locus. Monosomic mice are viable, fertile and are significantly smaller than wildtype (euploid) littermates from birth to adulthood. This mouse may be useful in studies of Down syndrome and further exploring the ploidy of DSCR/MMU16.

Development
A targeting vector containing a 3' portion of a neomycin resistance gene, a loxP site, and a hygromycin resistance gene at the (Cbr1) locus at the proximal end of MMU16 was electroporated into 129S6/SvEv-derived MC1 embryonic stem (ES) cells. Correctly targeted ES cells were then electroporated with a second targeting vector designed to orient a puromycin resistance gene, a loxP site, and a 5' portion of a neomycin resistance gene adjacent to the (Mx2) locus at the distal end of MMU16. Next, a CAGGS-cre expression vector was electroporated into ES cells harboring both targeted mutations. In ES cells where each construct inserted in trans on homologous chromosomes, recombination between the loxP sites resulted in mice with a duplication of the MMU16 region between the loxP sites on one homologous chromosome and interstitial deletion of the MMU16 region between the loxP sites on the other homologous chromosome. Heterozygous ES cells were injected into blastocysts and then transferred to surrogate mothers. F1 progeny of chimeric mice were bred to (C57BL/6J x C3H/HeJ)Fn to produce mice with segmental monosomy of MMU16 (Stock# 5654 -Del(16Cbr1-ORF9)1Rhr) or segmental trisomy (see Stock# 5383 -Dp(16Cbr1-ORF9)1Rhr). Monosomic mice were crossed with (C57BL/6J x C3H/HeJ)F1 for 4 generationsbefore arriving at The Jackson Laboratory. Upon arrival, this mutant strain has been maintained by breeding with B6C3F1/J.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Deletion

005535	B6.129S7-Del(11Cops3-Zfp179)1Jrl/J
003374	B6;129S2-H2dlAb1-Ea/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 Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Dp(16Cbr1-ORF9)1Rhr/0

        involves: 129S6/SvEvTac * C57BL/6

• nervous system phenotype
• decreased brain size (MGI Ref ID J:121764)
  • brain size is 85% of that in control mice
• small cerebellum (MGI Ref ID J:121764)
  • cerebellum size if 95% of that in control mice
• growth/size phenotype
• increased body size (MGI Ref ID J:93223)
• increased body weight (MGI Ref ID J:121764)
• skeleton phenotype
• abnormal mandible morphology (MGI Ref ID J:93223)
  • mandibles are overall enlarged
• enlarged skull (MGI Ref ID J:93223)
• long femur (MGI Ref ID J:93223)
• craniofacial phenotype
• abnormal mandible morphology (MGI Ref ID J:93223)
  • mandibles are overall enlarged
• enlarged skull (MGI Ref ID J:93223)
• limbs/digits/tail phenotype
• long femur (MGI Ref ID J:93223)

Dp(16Cbr1-ORF9)1Rhr/0

        B6.129S6-Dp(16Cbr1-ORF9)1Rhr

• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:121764)
  • mice perform similar to control mice in a Morris water maze with a visible or hidden platform and have normal long term potentials

View Research Applications

Research Applications

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

Developmental Biology Research
Growth Defects

Mouse/Human Gene Homologs
Down syndrome

Neurobiology Research
Behavioral and Learning Defects (Down syndrome)
Neurodegeneration (basal forebrain cholinergic neurons) (Down syndrome)

Research Tools
Developmental Biology Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Del(16Cbr1-ORF9)1Rhr
Allele Name		deletion, chromosome 16, R H Reeves 1
Allele Type		Targeted (other)
Common Name(s)		Del1Rhr; Ms1Rhr;
Mutation Made By		Roger Reeves,   Johns Hopkins Univ. Schl. Med
Strain of Origin		129S6/SvEvTac
ES Cell Line Name		MC1
ES Cell Line Strain		129S6/SvEvTac
General Note		ES cell line = MC1. A line of mice with segmental monosomy for Chr 16 was derived from descendants of the chimeric founder.
Molecular Note		Deletion of a 3.9 Mb segment of Chr 16 was engineered by cre-mediated recombination between single loxP sites inserted into homologous chromosomes. This deleted segment contains mouse orthologs of 33 conserved and minimally conserved genes in the human Down syndrome critical region. [MGI Ref ID J:93223]

Genotyping

Genotyping Information

Genotyping Protocols

Del(16Cbr1-ORF9)1Rhr, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Olson LE; Richtsmeier JT; Leszl J; Reeves RH. 2004. A chromosome 21 critical region does not cause specific down syndrome phenotypes. Science 306(5696):687-90. [PubMed: 15499018]  [MGI Ref ID J:93223]

Additional References

Del(16Cbr1-ORF9)1Rhr related

Olson LE; Roper RJ; Sengstaken CL; Peterson EA; Aquino V; Galdzicki Z; Siarey R; Pletnikov M; Moran TH; Reeves RH. 2007. Trisomy for the Down syndrome 'critical region' is necessary but not sufficient for brain phenotypes of trisomic mice. Hum Mol Genet 16(7):774-82. [PubMed: 17339268]  [MGI Ref ID J:121764]

Sussan TE; Yang A; Li F; Ostrowski MC; Reeves RH. 2008. Trisomy represses Apc(Min)-mediated tumours in mouse models of Down's syndrome. Nature 451(7174):73-5. [PubMed: 18172498]  [MGI Ref ID J:131046]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, monosomic mice are bred to wildtype B6C3F1/J. Loss of reproductive function has been observed following backcross to C57BL/6J after only 2 generations. C57BL/6 is not recommended for use in breeding this strain.

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

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
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
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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.

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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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.

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