This invention concerns "knockout" animals, including mice, which have a deficit of functional steroid hormone receptors, DNA constructs containing the mutations, and methods for producing the animals. The mutation is introduced into the animal or its ancestors at an embryonic stage. These knockout animals provide a model system for studying the biological role of hormones, including steroid hormones and sex steroids, in growth, development, morphological differentiation, and sexual and reproductive behavior and cycles, etc. More specifically, the animals may serve as models for testing sex hormones and synthetics that mimic or antagonize sex hormones for use in birth control methods or as hormone replacement therapies. In addition, they provide a system for the characterization of materials suspected of precipitating or conferring protection against osteoporosis, cardiovascular disease, breast cancer, endometrial cancer, and other cancers.