Description

Strain Information

Former Names MK/ReJ Slc11a2mk/J    (Changed: 03-APR-08 ) Type Segregating Inbred; Type Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation F85p+F7p+F2p

Control Information

	Control
	Untyped from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Slc11a2^mk/Slc11a2^mk

        MK/ReJ

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:98088)
  • only 10% survive to weaning on the MK/ReJ background
• homeostasis/metabolism phenotype
• abnormal iron homeostasis (MGI Ref ID J:100202)
  • decrease in total iron uptake and a decrease in the incorportation of iron into heme by reticulocytes
  • intraerythroid defects in iron metabolism with the erythrocyte zinc protoporphrin IX to heme (Znpp/H) ratio increased by 3.2 fold

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Slc11a2^mk/Slc11a2^mk

        129S6.MK-Slc11a2^mk

• life span-post-weaning/aging
• *normal* life span-post-weaning/aging (MGI Ref ID J:98088)
  • nearly 100% survival to adulthood on a 129S6.Mk/ReJ background
• homeostasis/metabolism phenotype
• increased liver iron level (MGI Ref ID J:98088)
  • liver non-heme iron levels higher than in knock-out mice
• liver/biliary system phenotype
• increased liver iron level (MGI Ref ID J:98088)
  • liver non-heme iron levels higher than in knock-out mice

Slc11a2^mk/Slc11a2^mk

        involves: C57BL/6J * DBA/2J * WB/Re

• hematopoietic system phenotype
• abnormal red blood cell (MGI Ref ID J:5985)
  • red blood cell protoporphyrin levels are higher than in controls
• homeostasis/metabolism phenotype
• increased porphyrin level (MGI Ref ID J:5985)
  • red blood cell protoporphyrin levels are higher than in controls

View Research Applications

Research Applications

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

Slc11a2^mk related

Hematological Research
Anemia, Iron Deficiency and Transport Defects (microcytic)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Slc11a2mk
Allele Name		microcytic anemia
Allele Type		Spontaneous
Common Name(s)		mk;
Strain of Origin		(C57BL/6J x DBA/2J)F2
Gene Symbol and Name		Slc11a2, solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2
Chromosome		15
Gene Common Name(s)		DCT1; DMT1; FLJ37416; NRAMP2; Nramp2; microcytic anemia; microcytic anemia, viable anaemia; mk; natural resistance-associated macrophage protein 2; van;
General Note		Homozygotes are recognizable by their pallor at birth. The red cells are smaller than normal and hypochromic from 15 days of gestation onward, but they are present in normal or greater than normal numbers (J:5167). Viability and fertility may be reduced and, on some genetic backgrounds, skin lesions occur early in life (J:5236). The anemia appears to be due to a generalized impairment of cellular iron uptake involving transfer of iron from the intestinal lumen to the mucosa as well as from plasma to erythroblasts (J:5293, J:5555, J:5306). Increased levels of free erythrocyte protoporphyrin have been reported in mice with microcytic anemia (J:31039). This mutation has been identified as missense mutation of Slc11a2, thus identifying Slc11a2 as an iron transport gene (J:42052). Microcytic anemia had been reported as a mutation in the Nfe2 nuclear DNA-binding protein gene, on the basis of an amino acid substitution in Nfe2 in microcytic anemia mice. However, non-anemic mice of a different inbred strain were also shown to have the same substitution (J:11821), and it was also shown that the anemia was not corrected by insertion of a wild-type Nfe2 transgene (J:22119).
Molecular Note		A glycine to arginine missense mutation resulting from a G to A transition within codon 185 has been associated with the observed phenotype. The mutation disrupts a critical transmembrane domain in the encoded protein. [MGI Ref ID J:42052]

Genotyping

Genotyping Information

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

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Salazar J; Mena N; Hunot S; Prigent A; Alvarez-Fischer D; Arredondo M; Duyckaerts C; Sazdovitch V; Zhao L; Garrick LM; Nunez MT; Garrick MD; Raisman-Vozari R; Hirsch EC. 2008. Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease. Proc Natl Acad Sci U S A 105(47):18578-83. [PubMed: 19011085]  [MGI Ref ID J:141521]

Slc11a2^mk related

Bannerman RM. 1976. Genetic defects of iron transport. Fed Proc 35(11):2281-5. [PubMed: 782924]  [MGI Ref ID J:5681]

Bannerman RM; Edwards JA; Kreimer-Birnbaum M; McFarland E; Russell ES. 1972. Hereditary microcytic anaemia in the mouse; studies in iron distribution and metabolism. Br J Haematol 23(2):235-45. [PubMed: 5070129]  [MGI Ref ID J:5293]

Bernstein SE. 1969. Hereditary disorders of the rodent erythron. In: Genetics in Laboratory Animal Medicine. Natl Acad Sci Publ, Washington, DC.  [MGI Ref ID J:30699]

Canonne-Hergaux F; Fleming MD; Levy JE; Gauthier S; Ralph T; Picard V; Andrews NC; Gros P. 2000. The Nramp2/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border. Blood 96(12):3964-70. [PubMed: 11090085]  [MGI Ref ID J:106634]

Canonne-Hergaux F; Levy JE; Fleming MD; Montross LK; Andrews NC; Gros P. 2001. Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders. Blood 97(4):1138-40. [PubMed: 11159549]  [MGI Ref ID J:67402]

Canonne-Hergaux F; Zhang AS; Ponka P; Gros P. 2001. Characterization of the iron transporter DMT1 (NRAMP2/DCT1) in red blood cells of normal and anemic mk/mk mice. Blood 98(13):3823-30. [PubMed: 11739192]  [MGI Ref ID J:115416]

Edwards JA; Hoke JE. 1975. Red cell iron uptake in hereditary microcytic anemia. Blood 46(3):381-8. [PubMed: 807277]  [MGI Ref ID J:5555]

Fleming MD; Trenor CC 3rd; Su MA; Foernzler D; Beier DR; Dietrich WF ; Andrews NC. 1997. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat Genet 16(4):383-6. [PubMed: 9241278]  [MGI Ref ID J:42052]

Gunshin H; Fujiwara Y; Custodio AO; Direnzo C; Robine S; Andrews NC. 2005. Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J Clin Invest 115(5):1258-1266. [PubMed: 15849611]  [MGI Ref ID J:98088]

Harrison DE. 1972. Marrow transplantation and iron therapy in mouse hereditary microcytic anemia. Blood 40(6):893-901. [PubMed: 4563452]  [MGI Ref ID J:5306]

Kreimer-Birnbaum M; Bannerman RM; Russell ES; Bernstein SE. 1972. Pyrrole pigments in normal and congenitally anaemic mice (+:+, W-W v , ha-ha, nb-nb, mk-mk, f-f and sla-Y). Comp Biochem Physiol A 43(1):21-30. [PubMed: 4404581]  [MGI Ref ID J:31039]

Levy JE; Montross LK; Andrews NC. 2000. Genes that modify the hemochromatosis phenotype in mice [see comments] J Clin Invest 105(9):1209-16. [PubMed: 10791995]  [MGI Ref ID J:62112]

Ludwiczek S; Theurl I; Muckenthaler MU; Jakab M; Mair SM; Theurl M; Kiss J; Paulmichl M; Hentze MW; Ritter M; Weiss G. 2007. Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1. Nat Med 13(4):448-54. [PubMed: 17293870]  [MGI Ref ID J:121724]

McFarland EC; Russell ES. 1975. Microcytic anemia (mk) near Ca on Chr 15. Mouse News Lett 53:35.  [MGI Ref ID J:13684]

Ney PA; Farina SF; Bodine DM; Andrews NC; Orkin SH; Neinhuis AW. 1995. Microcytic anemia in mk/mk mice is not corrected by retroviral-mediated gene transfer of wild-type p45 NF-E2. Exp Hematol 23(1):74-80. [PubMed: 7995373]  [MGI Ref ID J:22119]

Ohgami RS; Campagna DR; Antiochos B; Wood EB; Sharp JJ; Barker JE; Fleming MD. 2005. nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse. Blood 106(10):3625-31. [PubMed: 15994289]  [MGI Ref ID J:100202]

Peters LL; Andrews NC; Eicher EM; Davidson MB; Orkin SH; Lux SE. 1993. Mouse microcytic anaemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2 [published erratum appears in Nature 1994 Sep 22;371(6495):358] Nature 362(6422):768-70. [PubMed: 8469289]  [MGI Ref ID J:11821]

Russell ES; Bernstein SE. 1966. Blood and Blood Formation. In: Biology of the Laboratory Mouse. McGraw Hill, New York.  [MGI Ref ID J:24829]

Russell ES; McFarland EC; Kent EL. 1970. Low viability, skin lesions, and reduced fertility associated with microcytic anemia in the mouse. Transplant Proc 2(1):144-51. [PubMed: 5521744]  [MGI Ref ID J:5236]

Russell ES; Nash DJ; Bernstein SE; Kent EL; McFarland EC; Matthews SM; Norwood MS. 1970. Characterization and genetic studies of microcytic anemia in house mouse. Blood 35(6):838-50. [PubMed: 5427253]  [MGI Ref ID J:5167]

Salazar J; Mena N; Hunot S; Prigent A; Alvarez-Fischer D; Arredondo M; Duyckaerts C; Sazdovitch V; Zhao L; Garrick LM; Nunez MT; Garrick MD; Raisman-Vozari R; Hirsch EC. 2008. Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease. Proc Natl Acad Sci U S A 105(47):18578-83. [PubMed: 19011085]  [MGI Ref ID J:141521]

Sassa S; Bernstein SE. 1978. Studies of erythrocyte protoporphyrin in anemic mutant mice: use of a modified hematofluorometer for the detection of heterozygotes for hemolytic disease. Exp Hematol 6(5):479-87. [PubMed: 658175]  [MGI Ref ID J:5985]

Suzuki T; Momoi K; Hosoyamada M; Kimura M; Shibasaki T. 2008. Normal cadmium uptake in microcytic anemia mk/mk mice suggests that DMT1 is not the only cadmium transporter in vivo. Toxicol Appl Pharmacol 227(3):462-7. [PubMed: 18076961]  [MGI Ref ID J:135448]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of 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

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

Control Information

	Control
	Untyped 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
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

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.

No Liability

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.