Severe pallor is a distinguishing feature of Hk1dea homozygotes and is evident at birth. Decreased hexokinase activity is found in the spleen, kidney, and red blood cells, but not the liver. Peripheral blood smears reveal anisocytosis, hypochromia, polychromatophilia, in addition to the presence of echinocytes and a morphologic anomaly of red cells deemed "split cell" in which they pull into halves tethered by thin strands of membrane. Spheroctyes are not found. These homozygotes are smaller than normal, die prematurely, and females are infertile. The phenotype includes reduced red blood cell count, hemoglobin, hematocrit, and red blood cell mean corpuscular hemoglobin content. Circulating reticuloctyes are 83% rather than the normal 3.1%, red blood cell mean corpuscular volume is increased, and total bilirubin is increased. Splenic weight is increased, the red pulp is enlarged, and there is heightened iron accumulation in the kidney tubules and liver but not in the spleen. Consistent with the defect stemming from the erythroid cells, bone marrow transplantation from Hk1dea homozygotes into normal mice transfers all aspects of the disease. This mouse offers a model for human nonshperocytic hemolytic anemia, a disease caused by defects in human HK1 and presenting a comparable phenotype. (Peters et al., 2001.)
The Hk1dea mutation arose spontaneously in a mutant strain on the A/J background at The Jackson Laboratory. That background mutation was bred out and Hk1dea maintained via ovarian transplant-cross-intercross. Hk1dea remained on the A/J background and embryos were generated for cryopreservation from heterozygous females bred to heterozygous males.
|Allele Name||downeast anemia|
|Gene Symbol and Name||Hk1, hexokinase 1|
|Strain of Origin||A/J|
|Molecular Note||A spontaneous insertion of an early transposon sequence (ETn) in intron 4 of the gene was detected by Southern blot analysis and by sequencing. Northern blot analysis on RNA derived from spleen tissue of homozygous mice did not detect a wild-type size transcript, but trace amounts of a larger transcript were detected. Reduced hexokinase activity was shown functionally in red blood cells, spleen and kidney.|
Because homozygotes are fragile and die early, this strain is maintained by transplanting ovaries from a homozygote into an A.B-Tyr+ host (Stock# 002565) then breeding to A/J males. The obligate heterozygous offspring are intercrossed and generate A/J-Hk1dea/J homozygous females that are then donors for the next ovarian transplant generation.
When using the downeast anemia mouse strain in a publication, please cite the originating article(s) and include JAX stock #002768 in your Materials and Methods section.