Transgenic mice overexpressing foreign whey acidic protein (WAP) genes driven by metallothionein promoter

Our previous studies demonstrated that the gene coding for whey acidic protein (WAP) is expressed in a variety of tissues other than mammary glands in lactating mice (Wen et al., 1995). It was suspected, therefore, that WAP plays important physiological roles in tissues of rodents. To clarify biological functions of mouse WAP (mWAP), we produced transgenic mice introducing a 6.4 kb metallothionein-I (mMT-I)/mWAP construct where 1.8 kb mouse MT-I promoter was linked to 4.6 kb WAP structural gene. Three male mice were confirmed to be transgenic by Southern blot and PCR analyses, and served as the founders transmitting the genes to their offspring. The founders, their offspring and normal mice (control) were given drinking-water containing 25 mM ZnSO4 for 4 weeks. The expression levels of WAP genes induced by Zn2+ were about 3 times higher in the liver of transgenic mice than those of normal mice. Unexpectedly, it turned out that the expression of the endogenous WAP was also enhanced by the prolonged exposure to Zn2+. Despite the enhanced expression of WAP, no alteration in phenotypes, e.g., morphological characteristics, growth rates, reproductive performance and/or behavior have so far been detected in all the transgenic mice examined.