Description

Strain Information

Former Names BALB/cJ-Trfhpx/J    (Changed: 15-DEC-04 ) BALB/cJ-Trfhpx/JHmsJ    (Changed: 15-DEC-04 ) Type Coisogenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse H2 Haplotype d Generation F?N1p

Appearance
albino, unaffected
Related Genotype: A/A Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c

Description
Mice homozygous for the hpx allele exhibit refractory iron-deficient, hypochromic, microcytic anemia with iron-loading in the liver, pancreas, heart and brain. Homozygotes usually die within 2 weeks after birth with hypochromic anemia and very low serum transferrin. The mutant condition is evident in 13-day embryos, which have severe transferrin deficiency and hepatic iron loading. Heterozygotes have normal blood values but half normal concentrations of transferrin and show minor increases in iron stores. The condition closely resembles human atransferrinemia.

Development
The hypotransferrinemia with hemochromatosis (Trf^hpx) mutation arose spontaneously in the BALB/cJ inbred strain at The Jackson Laboratory (TJL) and was first reported by Dr. Seldon E. Bernstein in 1986. The mutation became extinct at TJL, but the original strain has been maintained at other institutions. Dr. Jerry Kaplan, at the University of Utah School of Medicine, obtained mice of this strain from Dr. Bernstein, then at TJL, many years ago. The strain was eventually transferred from Dr. Kaplan to Dr. Mark D. Fleming, at Harvard University and Children's Hospital, Boston. Dr. Fleming donated mice from his colony to TJL in November 2002. The line derived from Dr. Fleming's mice is designated BALB/cJ-Trf^hpx/BnUthHmsJ to reflect its history and to distinguish it from the line originally maintained at The Jackson Laboratory, called BALB/cJ-Trf^hpx (Stock No. 1188), from which DNA was preserved before it became extinct.

Control Information

	Control
	+/+ from the colony
	Heterozygote from the colony
	Untyped from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Atransferrinemia - 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

Trf^hpx/Trf⁺

        BALB/cJ-Trf^hpx

• hematopoietic system phenotype
• *normal* hematopoietic system phenotype (MGI Ref ID J:64456)
  • normal blood values
• homeostasis/metabolism phenotype
• abnormal iron homeostasis (MGI Ref ID J:64456)
• hemochromatosis (MGI Ref ID J:8936)
  • mild
• hypoferremia (MGI Ref ID J:64456)
  • progressive hyperferremia, but milder and later in life than homozygotes

Trf^hpx/Trf^hpx

        BALB/cJ-Trf^hpx

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:64456)
  • injections of transferrin extended life for at least 600 days
• lethality-postnatal
• postnatal lethality (MGI Ref ID J:8936)
  • death by 14 days of age
  • injections of purified transferrin, mouse or human serum exteneded life
• growth/size phenotype
• postnatal growth retardation (MGI Ref ID J:8936)
• hematopoietic system phenotype
• abnormal reticulocyte morphology (MGI Ref ID J:8936)
  • microreticulocytes
• anisocytosis (MGI Ref ID J:8936)
• decreased erythrocyte cell number (MGI Ref ID J:8936)
• decreased hematocrit (MGI Ref ID J:8936)
• decreased hemoglobin content (MGI Ref ID J:8936)
• decreased mean corpuscular hemoglobin concentration (MGI Ref ID J:64456)
• decreased mean corpuscular volume (MGI Ref ID J:8936)
• hypochromic anemia (MGI Ref ID J:64456)
• poikilocytosis (MGI Ref ID J:8936)
• spherocytosis (MGI Ref ID J:8936)
• homeostasis/metabolism phenotype
• abnormal iron homeostasis (MGI Ref ID J:8936)
  • increased clearance rates
  • increased clearance rate
• hemochromatosis (MGI Ref ID J:8936)
  • with iron loading visible in the liver, heart, kidney and pancreas
  • with iron loading, visible in the embryonic liver and at 6 months of age in the heart, kidney and pancreas
• hypoferremia (MGI Ref ID J:64456)
  • progressive hyperferremia

View Research Applications

Research Applications

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

Trf^hpx related

Hematological Research
Anemia, Iron Deficiency and Transport Defects (hemochromatosis)
Anemia, Iron Homeostasis Defects

Internal/Organ Research
Liver Defects (hemochromatosis)

Mouse/Human Gene Homologs
Atransferrinemia
Susceptibility to Iron Deficiency Anemia

Genes & Alleles

Gene & Allele Information

Allele Symbol		Trfhpx
Allele Name		hypotransferrinemia with hemochromatosis
Allele Type		Spontaneous
Common Name(s)		HP; hpx; hypotransferrinemic;
Strain of Origin		BALB/cJ
Gene Symbol and Name		Trf, transferrin
Chromosome		9
Gene Common Name(s)		AI266983; DKFZp781D0156; HP; MGC93500; PRO1557; PRO2086; Tfn; expressed sequence AI266983; hpx; hypotransferrinemia with hemochromatosis;
Molecular Note		A G-to-A point mutation at the splice donor site of exon 16 results in a 27 bp in-frame deletion in the transript. A small amount of mutant protein is detectable. [MGI Ref ID J:63638]

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

Bernstein SE. 1987. Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia. J Lab Clin Med 110(6):690-705. [PubMed: 3681112]  [MGI Ref ID J:8936]

Dickinson TK; Connor JR. 1995. Cellular distribution of iron, transferrin, and ferritin in the hypotransferrinemic (Hp) mouse brain. J Comp Neurol 355(1):67-80. [PubMed: 7636015]  [MGI Ref ID J:24976]

Dickinson TK; Connor JR. 1994. Histological analysis of selected brain regions of hypotransferrinemic mice. Brain Res 635(1-2):169-78. [PubMed: 8173952]  [MGI Ref ID J:16482]

Dickinson TK; Connor JR. 1998. Immunohistochemical analysis of transferrin receptor: regional and cellular distribution in the hypotransferrinemic (hpx) mouse brain Brain Res 801(1-2):171-81. [PubMed: 9729367]  [MGI Ref ID J:49207]

Iancu TC; Shiloh H; Raja KB; Simpson RJ; Peters TJ; Perl DP; Hsu A; Good PF. 1995. The hypotransferrinaemic mouse: ultrastructural and laser microprobe analysis observations. J Pathol 177(1):83-94. [PubMed: 7472784]  [MGI Ref ID J:28914]

Raja KB; Simpson RJ; Peters TJ. 1994. Intestinal iron absorption studies in mouse models of iron-overload. Br J Haematol 86(1):156-62. [PubMed: 8011525]  [MGI Ref ID J:16302]

Raja KB; Simpson RJ; Peters TJ. 1995. Plasma clearance of transferrin in control and hypotransferrinaemic mice: implications for regulation of transferrin turnover. Br J Haematol 89(1):177-80. [PubMed: 7833260]  [MGI Ref ID J:23013]

Simpson RJ; Konijn AM; Lombard M; Raja KB; Salisbury JR; Peters TJ. 1993. Tissue iron loading and histopathological changes in hypotransferrinaemic mice. J Pathol 171(3):237-44. [PubMed: 8277372]  [MGI Ref ID J:15825]

Trenor CC 3rd; Campagna DR; Sellers VM; Andrews NC; Fleming MD. 2000. The molecular defect in hypotransferrinemic mice. Blood 96(3):1113-8. [PubMed: 10910930]  [MGI Ref ID J:63638]

Yang F; Coalson JJ; Bobb HH; Carter JD; Banu J; Ghio AJ. 1999. Resistance of hypotransferrinemic mice to hyperoxia-induced lung injury. Am J Physiol 277(6 Pt 1):L1214-23. [PubMed: 10600893]  [MGI Ref ID J:59064]

Trf^hpx related

Bernstein SE. 1987. Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia. J Lab Clin Med 110(6):690-705. [PubMed: 3681112]  [MGI Ref ID J:8936]

Bernstein SE. 1986. hpx - hypotransferrinemia with hemochromatosis Mouse News Lett 75:29.  [MGI Ref ID J:64456]

Canonne-Hergaux F; Donovan A; Delaby C; Wang HJ; Gros P. 2006. Comparative studies of duodenal and macrophage ferroportin proteins. Am J Physiol Gastrointest Liver Physiol 290(1):G156-63. [PubMed: 16081760]  [MGI Ref ID J:104763]

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]

Dickinson TK; Connor JR. 1995. Cellular distribution of iron, transferrin, and ferritin in the hypotransferrinemic (Hp) mouse brain. J Comp Neurol 355(1):67-80. [PubMed: 7636015]  [MGI Ref ID J:24976]

Dickinson TK; Connor JR. 1994. Histological analysis of selected brain regions of hypotransferrinemic mice. Brain Res 635(1-2):169-78. [PubMed: 8173952]  [MGI Ref ID J:16482]

Dickinson TK; Connor JR. 1998. Immunohistochemical analysis of transferrin receptor: regional and cellular distribution in the hypotransferrinemic (hpx) mouse brain Brain Res 801(1-2):171-81. [PubMed: 9729367]  [MGI Ref ID J:49207]

Ghio AJ; Wang X; Silbajoris R; Garrick MD; Piantadosi CA; Yang F. 2003. DMT1 expression is increased in the lungs of hypotransferrinemic mice. Am J Physiol Lung Cell Mol Physiol 284(6):L938-44. [PubMed: 12576298]  [MGI Ref ID J:108632]

Gunshin H; Starr CN; Direnzo C; Fleming MD; Jin J; Greer EL; Sellers VM; Galica SM; Andrews NC. 2005. Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice. Blood 106(8):2879-83. [PubMed: 15961514]  [MGI Ref ID J:119528]

Iancu TC; Shiloh H; Raja KB; Simpson RJ; Peters TJ; Perl DP; Hsu A; Good PF. 1995. The hypotransferrinaemic mouse: ultrastructural and laser microprobe analysis observations. J Pathol 177(1):83-94. [PubMed: 7472784]  [MGI Ref ID J:28914]

Knutson MD; Levy JE; Andrews NC; Wessling-Resnick M. 2001. Expression of stimulator of Fe transport is not enhanced in Hfe knockout mice. J Nutr 131(5):1459-64. [PubMed: 11340100]  [MGI Ref ID J:69310]

Macedo MF; De Sousa M; Ned RM; Mascarenhas C; Andrews NC; Correia-Neves M. 2004. Transferrin is required for early T-cell differentiation. Immunology 112(4):543-9. [PubMed: 15270724]  [MGI Ref ID J:91471]

Malecki EA; Cook BM; Devenyi AG; Beard JL; Connor JR. 1999. Transferrin is required for normal distribution of 59Fe and 54Mn in mouse brain. J Neurol Sci 170(2):112-8. [PubMed: 10561526]  [MGI Ref ID J:58500]

Malecki EA; Devenyi AG; Beard JL; Connor JR. 1998. Transferrin response in normal and iron-deficient mice heterozygotic for hypotransferrinemia; effects on iron and manganese accumulation. Biometals 11(3):265-76. [PubMed: 9850571]  [MGI Ref ID J:113075]

Raja KB; Pountney DJ; Simpson RJ; Peters TJ. 1999. Importance of anemia and transferrin levels in the regulation of intestinal iron absorption in hypotransferrinemic mice. Blood 94(9):3185-92. [PubMed: 10556206]  [MGI Ref ID J:106636]

Raja KB; Simpson RJ; Peters TJ. 1994. Intestinal iron absorption studies in mouse models of iron-overload. Br J Haematol 86(1):156-62. [PubMed: 8011525]  [MGI Ref ID J:16302]

Raja KB; Simpson RJ; Peters TJ. 1995. Plasma clearance of transferrin in control and hypotransferrinaemic mice: implications for regulation of transferrin turnover. Br J Haematol 89(1):177-80. [PubMed: 7833260]  [MGI Ref ID J:23013]

Robb A; Wessling-Resnick M. 2004. Regulation of transferrin receptor 2 protein levels by transferrin. Blood 104(13):4294-9. [PubMed: 15319276]  [MGI Ref ID J:115489]

Simpson RJ; Konijn AM; Lombard M; Raja KB; Salisbury JR; Peters TJ. 1993. Tissue iron loading and histopathological changes in hypotransferrinaemic mice. J Pathol 171(3):237-44. [PubMed: 8277372]  [MGI Ref ID J:15825]

Takeda A; Takatsuka K; Connor JR; Oku N. 2001. Abnormal iron accumulation in the brain of neonatal hypotransferrinemic mice. Brain Res 912(2):154-61. [PubMed: 11532431]  [MGI Ref ID J:72173]

Takeda A; Takatsuka K; Connor JR; Oku N. 2002. Abnormal iron delivery to the bone marrow in neonatal hypotransferrinemic mice. Biometals 15(1):33-6. [PubMed: 11860021]  [MGI Ref ID J:113074]

Trenor CC 3rd; Campagna DR; Sellers VM; Andrews NC; Fleming MD. 2000. The molecular defect in hypotransferrinemic mice. Blood 96(3):1113-8. [PubMed: 10910930]  [MGI Ref ID J:63638]

Yang F; Coalson JJ; Bobb HH; Carter JD; Banu J; Ghio AJ. 1999. Resistance of hypotransferrinemic mice to hyperoxia-induced lung injury. Am J Physiol 277(6 Pt 1):L1214-23. [PubMed: 10600893]  [MGI Ref ID J:59064]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry

Despite their severe transferrin deficiency, homozygous mice treated with transferrin injections or red blood cell transfusions can survive after weaning. Homozygous females do not breed. An occasional homozygous male, with "robust transferrin replacement therapy," will prove fertile. Investigator recommends maintaining colony as heterozygote x heterozygote matings. Carriers may be identified by measurement of serum transferrin levels or PCR assay.

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.

Control Information

	Control
	+/+ from the colony
	Heterozygote from the colony
	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

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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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Terms of Use

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General Terms and Conditions

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

JAX^® Mice & Services Conditions of Use

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