Homozygotes have spherocytic hemolytic anemia and neonatal jaundice. Erythrocytes have diminished biconcavity, a smaller than normal diameter, increased density, an appearance of exovesiculation, and a short lifespan. At birth homozygotes are very pale then become yellow during the first few hours of life and die generally within a day of being born. Although it is rare for a spherocytosis homozygote to survive beyond one day of birth on the WB/Re or C57BL/6J (stock #000450) congenic background, homozygotes on the (C57BL/6J x WB/Re)F1 background are much more robust and the majority survive to adulthood. Those that make it to wean age are expected to have a reasonable lifespan, sometimes living as long as a year. Thus, most studies of this mutation in the adult have been done on the (C57BL/6J x WB/Re)F1 background. These homozygotes display diminished hematocrit, decreased red blood cell count, very elevated red blood cell protoporphyrin levels, increased erythropoiesis, reticulocytosis, hyperbilirubinaemia, cardiomegaly, hepatomegaly, and severe splenomegaly predominantly due to increased red pulp. Large areas of splenic necrosis and fibrosis develop. Thrombi can be found in the atrioventricular valves or within the atria of adults and infarcts have been observed in the myocardium and in the cerebrum, hippocampus, and cerebellum. Iron accumulates in the liver and kidneys, blood urea nitrogen levels become high, and hydronephrosis and membranoproliferative glomerulonephritis are found. By 2 to 3 months of age the urine becomes green due to hemosiderin and ferritin laden renal tubular cells and the urine later becomes red. Kaysser et al. posited that the likely cause of death in adult homozygotes is renal failure.
The spherocytosis mutation arose spontaneously in 1959 at the University of British Columbia Central Animal Depot in the progeny of an unpedigreed stock from Rockland Farms, reported to be C3H. This mutation was imported into The Jackson Laboratory before 1970 and backcrossed onto the C57BL/6J and WB/Re backgrounds by Dr. Elizabeth Russell and Dr. Seldon Bernstein. In 1970 this congenic was at backcross generation N2, in 1976 it reached N9, in 1986 it reached N21 and was subsequently passed into the care of Dr. Jane Barker. In 2010 sperm were cryopreserved from heterozygous males at generation N66.
|Gene Symbol and Name||Spta1, spectrin alpha, erythrocytic 1|
|Strain of Origin||C3H|
|General Note||This original spherocytosis mutation arose in an unpedigreed C3H stock.|
|Molecular Note||The mutation in the sph mouse was identified as a single base pair deletion in exon 11 that causes a frame shift and premature stop codon.|