B6.Cg-Ank1^nb/BrkJ

Stock number: 000448
Product name: B6-normoblastic anemia
Research areas: Hematological Research, Internal/Organ Research, Neurobiology Research

Description

These mice carry a spontaneous mutation at the Ank1 locus characterized by severe normocytic hypochromic anemia.

Detailed description

Normoblastosis homozygotes have a severe normocytic hypochromic anemia and can be identified at birth, or soon thereafter, by their bright orange color, which fades as they mature. They have elevated serum bilirubin and greatly increased fecal urobilinogen and the serum and urine remain highly colored even as the overall body color fades. Homozygotes are smaller than their wildtype and heterozygous siblings and display hepatomegaly, cardiac hypertrophy, marrow hyperplasia, leukocytosis, pronounced splenomegaly and enlarged lymph nodes. Nevertheless, the majority of homozygotes survive to adulthood. Immature red blood cells can be found in high numbers in the peripheral blood, and red cells are hypchromic although of normal or slightly elevated mean cell volume. In addition to hematopoietic defects this ankyrin 1 hypomorph also displays Purkinje cell degeneration such that there is a 50% loss of Purkinje cells at 6 months of age and concomitant tremors and unbalanced gait (Peters et al., 1991). More than half of homozygotes on a WBB6F1 hybrid background have been reported to develop calcium bilirubinate pigment gallstones after 6 months of age, with luminal gallstones occurring twice as frequently in females as in males (Trotman et al., 1980).

Development

The normoblastic anemia mutation arose spontaneously in late 1965 in a heterogeneous stock maintained by Dr. Katherine Hummel at The Jackson Laboratory. Dr. Seldon Bernstein and then Dr. Jane Barker backcrossed this mutation onto the C57BL/6J and WB/Re (stock #000453) backgrounds by repeated backcross-intercross breeding. In 1974 this strain reached generation N16, in 1986 N34, and 2001 embryos were generated for cryopreservation from C57BL/6J females bred to heterozygous males at generation N56.

Allele

Symbol: Ank1^nb
Name: normoblastic anemia
MGI accession ID: MGI:1856298
Generation method: Spontaneous
Attributes: Hypomorph
Marker symbol: Ank1
Marker name: ankyrin 1, erythroid
Chromosome: 8
Strain of origin: Non-inbred stock
Molecular note: This mutation arose in 1965 in a heterogeneous stock of mice maintained by Katherine P. Hummel at The Jackson Laboratory. A guanosine residue at position 4367 is deleted in exon 36 resulting in a frame shift mutation that introduces a premature stop 13 codons downstream and produces a truncated but functional protein.