These Hfe2 knockout mice exhibit iron loading and have applications in studies of juvenile or Type2A hemochromatosis, iron homeostasis and iron-induced oxidative damage.
Nancy C. Andrews, Duke University School of Medicine
Hfe2, hemochromatosis type 2 (juvenile) (human homolog), is involved in regulation of intestinal iron absorption. Mice that are homozygous for this targeted mutation are viable, fertile, normal in size and recapitulate some of the symptoms of human Type 2A hemochromatosis or hereditary juvenile hemochromatosis. Type 2A hemochromatosis is a genetic disorder of iron hyperabsorption that results in severe early onset iron loading in tissues, as well as low hepcidin levels, hypogonadotropic hypogonadism, and cardiomyopathy. At 4 weeks of age, the livers of homozygotes are grossly brown. At 6 to 7 weeks of age, homozygotes exhibit up to 20-fold more non-heme iron in the liver, increased non-heme iron levels in the pancreas, heart, kidney and testis, and decreased non-heme iron levels in the spleen. Histological analysis reveals iron accumulation in hepatocytes (pericanicular), exocrine and endocrine pancreas, renal distal tubules, cells of the anterior pituitary, and in arteriolar endothelial cells of the testis. A diminished amount of iron is found in proximal duodenal enterocytes. Homozygotes have a decreased level of hepatic hepcidin mRNA, and increased ferroportin protein levels in intestinal basolateral membrane, hepatic and splenic macrophages when compared to controls. Serum levels of iron are also elevated. Homozygotes over the age of 18 months exhibit iron loading in the retina, with retinal pigment epithelium hyperplasia and loss of ganglion cells, compared to age-matched controls. Although levels of Bmp6 mRNA is elevated in liver of homozygous mice, bone morphogenetic protein (BMP) signaling is impaired in hepatocytes. 5 week old homozygous males on an iron depleted diet for 25 days exhibit approximately 7-fold greater hepatic non-heme iron level when compared to controls. Carbon tetrachloride (CCl4) induced liver damage and fibrosis occurs earlier and is more severe in homozygotes compared to wildtype controls. The Donating Investigator notes that the level of iron loading in mutant animals varies based on the iron content of the diet, breeding strategy, and other factors.
A targeting vector containing a NEO cassette replaced exon 3 and the coding portion of exon 4. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129S6/SvEvTac mice, and then backcrossed to 129S6/SvEvTac for more than 10 generations.
|Allele Name||targeted mutation 1, Nancy C Andrews|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Hfe2-; Hjv-|
|Gene Symbol and Name||Hfe2, hemochromatosis type 2 (juvenile)|
|Gene Synonym(s)||2310035L15Rik; 2310035L15Rik; 5230400G09Rik; 5230400G09Rik; AI414844; AI789733; DL-M; HFE2A; HJV; JH; RGM domain family, member C; RGMC; RIKEN cDNA 2310035L15 gene; RIKEN cDNA 5230400G09 gene; Rgmc; Rgmc; expressed sequence AI414844; expressed sequence AI789733; hemojuvelin|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Exon 3 and the coding sequence in exon 4 were replaced upon the insertion of a floxed neo cassette, therefore deleting most of the coding sequence for the protein.|
|Mutations Made By|| |
Nancy Andrews, Duke University School of Medicine
When maintaining a live colony, these mice can be bred as heterozygotes or homozygotes.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (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. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES 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 JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or SERVICES by JACKSON.