Homozygotes provide a molecular and phenotypic model of hereditary spherocytosis type 3 and a phenotypic model for hereditary spherocytosis type 1 and some aspects of sickle cell anemia. Most phenotypic assessment has been performed using F1 homozygous offspring of heterozygotes from the C57BL/6J and WB/Re congenic strains or homozygotes generated on a B6;WB segregating background. Approximately half die by 6 months of age. Homozygotes display hemolytic anemia with spherocytosis, microcytosis, reduced hematocrit, reticulocytisis, extramedullary hematopoiesis in the spleen and liver, lymphocytosis, neutrophilia, lymph node hyperlasia, and cardiac hypertrophy. Homozygotes can be identified within the first day of birth by their jaundiced color. Consequent to the underlying disorder, homozygotes are prone to developing gallstones, pneumonitis, and vaso-occulsive disease in multiple organs.
The hymolytic anemia mutation arose spontaneously in the DBA/1J inbred strain at The Jackson Laboratory in approximately 1960. This mutation was backcrossed onto the C57BL/6J and WB/Re inbred backgrounds by Seldon Bernstein. The C57BL/6J congenic reached generation N21 in 1968, N30 in 1970, N37 in 1978, N48 in 1986 and was subsequently transferred to the colony of Dr. Jane Barker. In 2001 sperm were cryopreserved from heterozygous males at generation N76.
|Allele Name||hemolytic anemia|
|Allele Synonym(s)||ha; sph1J; Sph-J|
|Gene Symbol and Name||Spta1, spectrin alpha, erythrocytic 1|
|Strain of Origin||DBA/1J|
|Molecular Note||The mutation in the sph-ha mouse (also known as sph-J) was identified as a C-to-A transversion in exon 52 that converts a tyrosine 2403 to a stop codon (p.Y2403*). This mutation truncates the protein by 13 amino acids.|