Effects of in vivo heregulin beta i treatment in wild-type and ErbB gene-targeted mice depend on receptor levels and pregnancy

Mice heterozygous (+/-) for either heregulin (HRG), ErbB2, or ErbB3 mere cr eated by gene targeting, resulting in the loss of one functional gene copy and an associated decrease in targeted protein. We examined the in vivo act ivity of recombinant HRG peptide, rHRG beta1 (amino acids 177 to 241), in t he three heterozygous mouse lines and in wild-type (WT) mice, both pregnant and nonpregnant, Nonpregnant WT and HRG(+/-) mice of both sexes were sensi tive to rHRG pi treatment as evidenced by a high mortality rate associated with abdominal enlargement and parietal cell loss. However, pregnant WT mic e and ErbB2 and ErbB3 heterozygous mice treated with rHRG pr were less affe cted, with significantly lower mortality rates and a less severe abdominal phenotype, Histological analysis revealed extensive breast ductal hyperplas ia in females of all genotypes after rHRG pi treatment. Hyperplasia of othe r epithelial tissues such as the pancreas and intestine and the growth of c ardiac nerve bundles were also observed, independent of sex.