These mice carry a spontaneous mutation at the Trf locus characterized by refractory iron-deficient, hypochromic, microcytic anemia with iron-loading in the liver, pancreas, heart and brain.Read More +
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.
The hypotransferrinemia with hemochromatosis (Trfhpx) 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-Trfhpx/BnUthHmsJ to reflect its history and to distinguish it from the line originally maintained at The Jackson Laboratory, called BALB/cJ-Trfhpx (Stock No. 001188), from which DNA was preserved before it became extinct.
|Allele Name||hypotransferrinemia with hemochromatosis|
|Allele Synonym(s)||HP; hpx; hypotransferrinemic|
|Gene Symbol and Name||Trf, transferrin|
|Strain of Origin||BALB/cJ|
|Molecular Note||A G-to-A point mutation in the first nucleotide of intron 16 eliminates exon 16 splice donor site C-GT by changing it to C-AT. This results in mis-splicing, including the use of a cryptic splice donor 27 bp upstream, deleting 9 codons. A small amount of mutant protein is detectable.|
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.
When using the hpx mouse strain in a publication, please cite the originating article(s) and include JAX stock #004546 in your Materials and Methods section.