The Murine Stanniocalcin 2 Gene Is a Negative Regulator of Postnatal Growth

Stanniocalcin (STC), a secreted glycoprotein, was first studied in fish as a classical hormone with a role in regulating serum calcium levels. There are two closely related proteins in mammals, STC1 and STC2, with functions that are currently unclear. Both proteins are expressed in numerous mammalian tissues rather than being secreted from a specific endocrine gland. No phenotype has been detected yet in Stc1-null mice, and to investigate whether Stc2 could have compensated for the loss of Stc1, we have now generated Stc2−/− and Stc1−/− Stc2−/− mice. Although Stc1 is expressed in the ovary and lactating mouse mammary glands, like the Stc1−/− mice, the Stc1−/− Stc2−/− mice had no detected decrease in fertility, fecundity, or weight gain up until weaning. Serum calcium and phosphate levels were normal in Stc1−/− Stc2−/− mice, indicating it is unlikely that the mammalian stanniocalcins have a major physiological role in mineral homeostasis. Mice with Stc2 deleted were 10–15% larger and grew at a faster rate than wild-type mice from 4 wk onward, and the Stc1−/− Stc2−/− mice had a similar growth phenotype. This effect was not mediated through the GH/IGF-I axis. The results are consistent with STC2 being a negative regulator of postnatal growth.