Adh7 (alcohol dehydrogenase 7 (class IV) or Adh4) knock-out mice exhibit an impaired ability to metabolize a number of substrates including retinol (vitamin A), ethanol and dopamine.
Gregg Duester, Burnham Institute for Medical Research
The Adh7 (alcohol dehydrogenase 7 (class IV) or Adh4) gene encodes an enzyme that functions to metabolize multiple substrates including ethanol and toxic aldehydes, but is most active as a retinol dehydrogenase converting retinol (vitamin A) to retinoic acid. Adh7 (Adh4) knock-out mice contain a neomycin cassette designed to replace the promoter and exons 1-6. Mice that are homozygous for the targeted mutation are viable and fertile with no overt phenotype. Homozygous females placed on a vitamin A deficient diet produce a higher number of stillbirths than wild-type mice. Mice treated with retinol have 8 fold lower levels of retinoic acid in the kidney. In addition, blood ethanol clearance is reduced following administration of ethanol to Adh4-/- mice. Administration of D-amphetamine or apomorphine results in increased levels of dopamine and DOPAC in the substantia nigra and may be associated with Parkinson's disease risk factors. These mice may be useful for studying retinoid, ethanol and dopamine metabolism.
The targeting vector is designed to replace the promoter and exons 1-6 containing the coding region for amino acid residues 1-275 with a neomycin resistance cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were crossed to Black Swiss females for germline transmission. Mice were then crossed to C57BL/6 mice for an unspecified number of generations. The strain was maintained on a mixed genetic background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.
|Allele Name||targeted mutation 1, Gregg Duester|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Adh7, alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A PGK-neo cassette replaced the promoter and exons 1 through 6. Northern blot analysis showed an absence of transcript in extracts isolated from the stomach and skin tissue of homozygous mutant mice. Western blot analysis confirmed a lack of encoded protein and normal levels of other alcohol dehydrogenases in homozygous mutant animals.|
When maintaining a live colony, these mice are bred by homozygous sibling matings.
When using the Adh4- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #50696 in your Materials and Methods section.