Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N1   Donating Investigator Zena Harris,   Johns Hopkins Univ School of Medicine

Description
Mice that are homozygous null for the Cp gene demonstrate a progressive accumulation of iron in hepatocytes and reticuloendothelial cells. By one year of age, iron content of the liver and spleen reaches three to six-fold that observed in wild-type litter mates. The Cp gene product appears to be necessary for proper iron efflux from these cell types. This strain represents a viable murine model for aceruloplasminemia. At one year of age there is no evidence of anemia, diabetes, or neurological symptoms despite iron accumulation at the corresponding tissue sites.

Development
The majority of exon 17 and exon 18 has been replaced with a neomycin cassette resulting in the generation of an unstable mRNA.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Aceruloplasminemia - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Cp^tm1Hrs/Cp^tm1Hrs

        involves: 129X1/SvJ * Black Swiss

• homeostasis/metabolism phenotype
• abnormal iron homeostasis (MGI Ref ID J:57730)
  • ferrokinetic studies showed normal rates of iron absorption, initial tissue iron distribution, and plasma iron turnover
  • no differences were detected in cellular iron uptake; however, homozygotes displayed a significant impairment in hepatocyte iron efflux
  • homozygotes showed elevated serum ferritin
• abnormal iron level (MGI Ref ID J:57730)
  • at 1 year of age, there was no evidence of diabetes, anemia, or neurological deficits despite iron accumulation in these sites
• increased liver iron level (MGI Ref ID J:71807)
  • hepatic iron displayed a 3.5-fold increase in aceruloplasminemic mice due to loss of ferroxidase function
  • progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the liver by 1 year of age
  • the liver displayed normal cellular architecture with abundant iron in reticuloendothelial cells
• increased spleen iron level (MGI Ref ID J:57730)
  • progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the spleen by 1 year of age
  • the spleen displayed normal cellular architecture with abundant iron in reticuloendothelial cells
• abnormal liver copper level (MGI Ref ID J:71807)
  • aceruloplasminemic mice showed normal copper gastrointestinal absorption, hepatic uptake, and biliary copper excretion
  • the copper content of brain, heart, spleen, and kidney was normal, and homozygotes exhibited normal copper-zinc superoxide dismutase activity in these tissues
  • notably, hepatic copper content was significantly elevated in aceruloplasminemic mice
• hematopoietic system phenotype
• *normal* hematopoietic system phenotype (MGI Ref ID J:57730)
  • the hemoglobin concentration remained normal relative to wild-type
• increased spleen iron level (MGI Ref ID J:57730)
  • progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the spleen by 1 year of age
  • the spleen displayed normal cellular architecture with abundant iron in reticuloendothelial cells
• liver/biliary system phenotype
• abnormal liver copper level (MGI Ref ID J:71807)
  • aceruloplasminemic mice showed normal copper gastrointestinal absorption, hepatic uptake, and biliary copper excretion
  • the copper content of brain, heart, spleen, and kidney was normal, and homozygotes exhibited normal copper-zinc superoxide dismutase activity in these tissues
  • notably, hepatic copper content was significantly elevated in aceruloplasminemic mice
• increased liver iron level (MGI Ref ID J:71807)
  • hepatic iron displayed a 3.5-fold increase in aceruloplasminemic mice due to loss of ferroxidase function
  • progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the liver by 1 year of age
  • the liver displayed normal cellular architecture with abundant iron in reticuloendothelial cells
• immune system phenotype
• increased spleen iron level (MGI Ref ID J:57730)
  • progressive accumulation of parenchymal iron, reaching a 3- to 6-fold increase in the iron content of the spleen by 1 year of age
  • the spleen displayed normal cellular architecture with abundant iron in reticuloendothelial cells

View Research Applications

Research Applications

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

Cp^tm1Hrs related

Hematological Research
Anemia, Iron Homeostasis Defects

Metabolism Research
Iron Metabolism

Mouse/Human Gene Homologs
aceruloplasminemia

Genes & Alleles

Gene & Allele Information

Allele Symbol		Cptm1Hrs
Allele Name		targeted mutation 1, Z Leah Harris
Allele Type		Targeted (knock-out)
Common Name(s)		Cp-;
Mutation Made By		Zena Harris,   Johns Hopkins Univ School of Medicine
Strain of Origin		129X1/SvJ
ES Cell Line Name		RW-4
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Cp, ceruloplasmin
Chromosome		3
Gene Common Name(s)		CERP; CP-2; D3Ertd555e; DNA segment, Chr 3, ERATO Doi 555, expressed; RATCERP;
Molecular Note		A neomycin resistance cassette replaced a genomic fragment containing part of exon 17, intron 17 and part of exon 18, which include sequences encoding the residues essential for the formation of the trinuclear copper cluster of the encoded protein. Western blot analysis on serum derived from homozygous mice demonstrated that no detectable encoded protein was present, and activity assays on serum of homozygous mice confirmed that no functional protein is made from this allele. [MGI Ref ID J:57730]

Genotyping

Genotyping Information

Genotyping Protocols

Cp^tm1Hrs, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Cp^tm1Hrs related

Cherukuri S; Potla R; Sarkar J; Nurko S; Harris ZL; Fox PL. 2005. Unexpected role of ceruloplasmin in intestinal iron absorption. Cell Metab 2(5):309-19. [PubMed: 16271531]  [MGI Ref ID J:129671]

Cherukuri S; Tripoulas NA; Nurko S; Fox PL. 2004. Anemia and impaired stress-induced erythropoiesis in aceruloplasminemic mice. Blood Cells Mol Dis 33(3):346-55. [PubMed: 15528156]  [MGI Ref ID J:95008]

Dunaief JL. 2006. Iron induced oxidative damage as a potential factor in age-related macular degeneration: the Cogan Lecture. Invest Ophthalmol Vis Sci 47(11):4660-4. [PubMed: 17065470]  [MGI Ref ID J:123093]

Hadziahmetovic M; Dentchev T; Song Y; Haddad N; He X; Hahn P; Pratico D; Wen R; Harris ZL; Lambris JD; Beard J; Dunaief JL. 2008. Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD. Invest Ophthalmol Vis Sci 49(6):2728-36. [PubMed: 18326691]  [MGI Ref ID J:136925]

Hahn P; Dentchev T; Qian Y; Rouault T; Harris ZL; Dunaief JL. 2004. Immunolocalization and regulation of iron handling proteins ferritin and ferroportin in the retina. Mol Vis 10:598-607. [PubMed: 15354085]  [MGI Ref ID J:93208]

Hahn P; Qian Y; Dentchev T; Chen L; Beard J; Harris ZL; Dunaief JL. 2004. Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration. Proc Natl Acad Sci U S A 101(38):13850-5. [PubMed: 15365174]  [MGI Ref ID J:92620]

Harris ZL; Durley AP; Man TK; Gitlin JD. 1999. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc Natl Acad Sci U S A 96(19):10812-7. [PubMed: 10485908]  [MGI Ref ID J:57730]

Meyer LA; Durley AP; Prohaska JR; Harris ZL. 2001. Copper transport and metabolism are normal in aceruloplasminemic mice. J Biol Chem 276(39):36857-61. [PubMed: 11461924]  [MGI Ref ID J:71807]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

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

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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	None Available
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

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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.

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Contact Information
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Terms of Use

Terms of Use

General Terms and Conditions

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Contact information

General inquiries

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

JAX^® Mice & Services Conditions of Use

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