B6.129S4-Tfrc^tm1Nca/J

Stock number: 018387
Product name: Tfrc KO , Trfr KO , TfR1 KO
Research areas: Developmental Biology Research, Hematological Research, Internal/Organ Research

Description

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.

Detailed description

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.

Development

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

Symbol: Tfrc^tm1Nca
Name: targeted mutation 1, Nancy C Andrews
MGI accession ID: MGI:1859944
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tfrc
Marker name: transferrin receptor
Chromosome: 16
Strain of origin: 129S4/SvJae
Molecular note: Coding sequence including exons 3 through 5 was replaced with a neomycin selection cassette.