Osteogenesis imperfecta in holstein calves

Abstract

An inherited disease resembling human osteogenesis imperfecta (OI) was diagnosed in Holstein calves in Texas. Although the progenitor bull was clinically normal and only 25% of its progeny were affected, dominant inheritance was confirmed by the birth of an affected calf in a cross-breeding study. The defective gene probably arose as a de novo gonadal mutation in the bull. Affected calves had marked bone fragility with multiple in utero and perinatal bone fractures, joint laxity, blue sclerae, and pink, friable teeth. Microscopically, there was marked hypoplasia of tendons, dentin, sclerae and skin, and defective bone apposition, resulting in osteopenia, and in some cases, multiple trabecular microfractures. Ultrastructurally, there was dilation of the rough endoplasmic reticulum in osteoblasts, odontoblasts and fibroblasts of sclerae, skin and tendons, and reduced collagen fibril diameter in sclerae, skin and tendons. Biochemical alterations included delayed electrophoretic migration of collagen (alpha) chains in extracts of bone, tendon and skin, and increased hydroxylation of lysine residues in type I collagen from bone. Arrested development of embryonic mesenchymal cells which produce type I collagen is suggested as a possible mechanism for the alterations observed in this disease. The clinical and morphological characteristics of this disease were similar, but not identical, to a disease reported in Holstein-Friesian cattle in Australia. These two bovine syndromes should prove to be valuable animal models of human OI.