The ENU-induced hem9 allele of Ube2o results from a nonsense point mutation and a loss-of-function mutation. Homozygous mice exhibit hypochromic, microcytic anemia associated with erythrocytosis and may be useful in studying proteomic remodeling in erythropoiesis.
Mark D Fleming, Children's Hospital Boston
Monica Justice, The Hospital for Sick Children (SickKids)
The targeted Ube2o gene encodes an E2-E3 hybrid ubiquitin-protein ligase.
These Ube2ohem9 chemically-induced (ENU) mutant mice carry the c.3361G>T/p.E1121X nonsense mutation, which results in truncation of the C-terminal 168 amino acids and loss-of-function mutation. No gene product (protein) is detected by western blot analysis of blood from homozygotes. Ribosome elimination during erythrocyte maturation is absent in mutant mice. TEM examination reveals inclusions in late stage reticulocytes. Mice that are homozygous for this mutant allele are viable and fertile.
These mutant mice were created by the laboratory of Dr. Monica Justice (Baylor College of Medicine) using multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder C57BL/6J mice. Genetic screening was utilized to identify mice with a metabolic and hematopoietic phenotype described as hypochromic, microcytic anemia associated with erythrocytosis. Using a candidate gene approach, a region of chromosome 11 containing the Ube2o gene was associated with the mutant phenotype. Sequencing of this gene identified a G to T substitution, p.E1121X nonsense mutation that is expected to generate a protein lacking the C-terminal 168 amino acids.
The mice were backcrossed to C57BL/6J for 20 generations.
Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
|Allele Name||haematopoietic 9|
|Allele Type||Chemically induced (ENU) (Null/Knockout)|
|Allele Synonym(s)||hem9; Ube2oE1121X|
|Gene Symbol and Name||Ube2o, ubiquitin-conjugating enzyme E2O|
|Strain of Origin||C57BL/6J|
|Molecular Note||This allele was identified in a screen for a metabolic and haematopoietic phenotype described as hypochromic, microcytic anemia associated with erythrocytosis using ENU-treated C57BL/6J males (G0). Sequencing identified a G to T substitution, resulting in a E1121X (changing glutamic acid to a termination codon) mutation in the Ube2o gene. The mutation causes truncation of the C-terminal 168 amino acids and is a loss-of-function mutation. No gene product (protein) is detected by western blot analysis of blood.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Ube2ohem9 mouse strain in a publication, please cite the originating article(s) and include JAX stock #029093 in your Materials and Methods section.
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