Welfare complications in the male BN/Crl and RjHan:SD rat streptozotocin-induced diabetes models

The streptozotocin (STZ)-induced hyperglycaemic rat model is widely used in diabetes research, particularly for investigating diabetic retinopathy; however, animal welfare concerns are often underreported. This study evaluated welfare outcomes in two commonly used rat lines, Brown Norway (BN/Crl) and Sprague Dawley (RjHan:SD). Data were collected from a series of diabetic retinopathy studies, in which a total of 183 BN/Crl and 76 RjHan:SD male rats received 40-65 mg/kg STZ via intraperitoneal injection and were monitored for 5-12 weeks. Welfare parameters, including body weight development and urologic complications (notably paraphimosis), were recorded and compared. Both lines achieved hyperglycaemia (≥16 mmol/l) within three weeks. However, BN/Crl rats exhibited a high incidence (82.5%) and severity of paraphimosis, along with marked weight loss, resulting in 13.7% of the animals reaching humane endpoint criteria for euthanasia. Weight loss positively correlated with STZ doses, with the highest dose (65 mg/kg) leading to 17.2% humane endpoint rate. In contrast, RjHan:SD rats exhibited significantly fewer urologic complications and maintained better weight gain, with none reaching humane endpoint. Our findings suggest that, while BN/Crl rats may offer advantages for ocular research owing to their pigmented eyes, their susceptibility to severe welfare issues raises concerns regarding their routine use. Furthermore, standardised supportive treatments, such as insulin supplementation, are worth considering for the model. This study highlights that careful selection of model animals, disease induction protocols and supportive treatments can optimise research outcomes and avoid loss of experimental animals, while adhering to the 3Rs.