Dr. Mario Capecchi and colleagues at the University of Utah and the Department of Veterans Affairs Medical Center (Salt Lake City, UT) have discovered that a gene called xanthine oxidoreductase, or XOR for short, is required for lactation in female mice. This previously unidentified role for XOR in lactation reveals a possible genetic basis for the lactation difficulties experienced by nearly 5% of women.
XOR was originally identified as encoding an enzyme involved in purine catabolism (the breakdown of adenine and guanine nucleotide bases). Because XOR is expressed in nearly all cells of the body and its protein product participates in a basic metabolic process fundamental to cell survival, XOR was labeled as a "housekeeping gene." But in addition to its constitutive expression patterns, XOR is also highly expressed in lactating mammary epithelium beginning in late pregnancy – prompting researchers to suspect an additional, and perhaps different, role for XOR in the lactating mammary gland.
To identify the function of XOR in the lactating mammary gland, Dr. Capecchi and colleagues generated mice lacking either one (heterozygous) or both (homozygous) functional copies of the XOR gene. As expected for homozygous mutants of a housekeeping gene, homozygous XOR-mutant mice died by 6 weeks of age. In contrast, though, the heterozygous XOR-mutant mice appeared normal, healthy and fertile, but first author Claudia Vorbach and colleagues soon noticed that pups from the XOR heterozygous females all died ~12 days postpartum. The researchers found that pups born to heterozygous XOR-mutant female mice – regardless of the pups XOR status – were essentially starving due to their mothers inability to maintain lactation.
Heather Cosel | EurekAlert!
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