Mice that are homozygous for this Tfrc knockout allele are embryonic lethal. Heterozygotes exhibit defective erythrocyte development and anemia. These mutant mice may be useful in studies of iron homeostasis, erythropoiesis and nervous system development.
Nancy C. Andrews, Duke University School of Medicine
The transferrin receptor is essential to cellular uptake of iron via endocytosis, and has a critical role in erythropoiesis and nervous system development. These mice carry a targeted mutation of the Tfrc, transferrin receptor, gene, in which a NEO cassette replaces exons 3 through 5. Mice that are heterozygous for the targeted mutation are viable and fertile. Homozygous null mice have an embryonic lethal phenotype, failing to develop past embryonic day 12.5, and exhibit severe anemia with hydrops fetalis, hypoxia, kinked neural tubes and pericardial effusions. Heterozygotes on the 129S6/SvEvTac background have decreased total body iron levels, erythroid microcytosis and hypochromia. Mutants on the 129S6/SvEvTac background have a compensatory increase in erythrocyte cell number that compensates for defective erythropoiesis and results in normal hematocrits
and hemoglobin levels.
The Donating Investigator reports preliminary phenotyping data that indicate heterozygotes on the C57BL/6J background display a compensatory increase in erythrocyte number, and that this increase may be insufficient to raise hemoglobin and hemocrit to normal levels.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing a NEO cassette was used to disrupt exons 3 through 5. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice. Heterozygotes were intercrossed to generate homozygotes. The mice were then backcrossed to C57BL/6J for 16 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Nancy C Andrews|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Tfrc, transferrin receptor|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Coding sequence including exons 3 through 5 was replaced with a neomycin selection cassette.|
|Mutations Made By|| |
Nancy Andrews, Duke University School of Medicine
When maintaining a live colony, these mice can be bred as heterozygotes. Homozygous null mice have an embryonic lethal phenotype, failing to develop past embryonic day 12.5.
When using the B6.129S4-Tfrctm1Nca/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018387 in your Materials and Methods section.