Mice that are homozygous for this Hmox1 (heme oxygenase (decycling) 1) targeted mutation develop anemia with diminished serum iron, increased serum ferritin, iron accumulation in kidney and liver and progressive chronic inflammatory disease. Homozygotes occur at a lower than expected frequency, or are not produced, from heterozygous crosses and have decreased postnatal survival. This mutant mouse strain may be useful in studies of hemochromatosis, inflammation and iron metabolism.
Raymond F. Burk, Vanderbilt UniversityRead More +
Mice that are homozygous for this targeted mutation are slightly smaller in size than wildtype littermates and exhibit poor grooming and hypoactivity. As early as 20 weeks of age, homozygotes develop anemia with diminished serum iron and increased serum ferritin. Histological analysis reveals iron accumulation in kidney and liver. Elevated oxidized proteins and lipid peroxidation develop in the liver and kidney. Homozygotes develop progressive chronic inflammatorydisease, including enlarged spleen and lymph nodes, inflammatory infiltrates, glomerulonephritis, fibrosis. Homozygous male mice have smaller testis than wildtype controls. Homozygotes occur at a lower than expected frequency, or are not produced, from heterozygous crosses and have decreased postnatal survival. An almost undetectable abnormal gene product (mRNA) is detected by Northern blot analysis of total splenic RNA. This mutant mouse strain may be useful in studies of hemochromatosis, inflammation and iron metabolism.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing PGK-neo cassette was used to disrupt 3.7kb of sequence containing exons 3, 4 and part of exon 5. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to FVB for 10 generations.
|Allele Name||targeted mutation 1, Kenneth D Poss|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||HO-1-; HO1-; Hmox1-|
|Gene Symbol and Name||Hmox1, heme oxygenase 1|
|Gene Synonym(s)||D8Wsu38e; D8Wsu38e; DNA segment, Chr 8, Wayne State University 38, expressed; HEOXG; HMOX1D; HO-1; HO1; HSP32; Heox; Hmox; Hmox; Ho-1; Ho1; Hsp32; bK286B10; hemoxygenase; hsp32|
|Strain of Origin||129S2/SvPas|
|General Note||Phenotypic Similarity to Human Syndrome: Iron overload disorders including Hemochromatosis and Anemia of chronic inflammation in homozygous mice (J:79254)|
|Molecular Note||A 3.7 kb fragment encompassing exons 3, 4, and a portion of 5 was replaced with a neomycin selection cassette. The deleted region consisted of approximately 85% of the coding region (226 residues). A low level of aberrantly spliced transcript was identified in homozygous mutant mice by Northern blot analysis of total splenic RNA.|
|Mutations Made By|| |
Kenneth Poss, Massachusetts Institute of Technology
When maintaining a live colony, these mice can be bred as heterozygotes. Fewer than expected or no homozygotes are produced from heterozygote crosses.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
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