Transplantation of Bovine Mammary Tissue to Athymic Nude Mice: Growth Subcutaneously and in Mammary Gland-Free Fat Pads

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Abstract
Mammary epithelium from five Holstein cows was transplanted as subcutaneous slices and as collagenase dissociated epithelial cells into mammary gland free-fat pads of athymic nude mice. Two weeks posttransplantation, mice were injected daily for 20 d with saline, 17.beta.-estradiol plus progesterone, or 17.beta.-estradiol plus progesterone plus growth hormone plus prolactin. In a second experiment, mice were treated with saline, cholera toxin, 17.beta.-estradiol (subcutaneous pellet of 2 mg 17.beta.-estradiol and 38 mg cholesterol), or 17.beta.-estradiol plus cholera toxin. In each experiment mammary slices maintained normal morphology. Growth of epithelium within slices ([3H]thymidine autoradiography) was increased 167% by estradiol plus progesterone 264% by estradiol plus progesterone plus growth hormone plus prolactin, 90% by estradiol, 60% by cholera toxin, and 137% by estradiol plus cholera toxin. Cells injected into mammary gland free fat pads formed hollow, multilayered, spherical "organoids". Organoid area was increased 47% by estradiol plus progesterone, 189% by estradiol plus progesterone plus growth hormone plus prolactin, 72% by estradiol, 86% by cholera toxin and 74% by estradiol plus cholera toxin. Thus, athymic nude mice appear suitable for the ex vivo in vivo study of bovine mammary epithelial growth and differentiation.