Critical care and survival of fragile animals: The case of Prrxl1 knockout mice

Abstract

The generation of genetically modified animal models in which a given gene is permanently deleted or overexpressed, sometimes results in fragile phenotypes characterized by high morbidity and premature death. This undesired outcome creates important welfare difficulties and poses a huge limitation in the usefulness of animal models for long term physiological studies; the ultimate goal of knockout animal models is to study the role of a modified gene in adult animals. In our research we study a transgenic mouse model with a deletion of the Prrxl1 gene, a transcription factor crucial for the correct development of spinal and ganglionar nociceptive neurons. However, Prrxl1 (paired-related homeobox protein-like 1) knockout animals are smaller than wild-type littermates and show signs of difficulty in feeding behaviour that lead to a very low post-weaning survival rate. In this paper we describe the efficacy in the reduction of the post weaning lethality observed in Prrxl1−/− animals by the introduction of simple modifications in the housing and feeding protocol of the colony. We were able to obtain a survival rate close to 80% over a one year period. We also evaluated some characteristics of the Prrxl1 phenotype, namely grooming behaviour, response to pain stimulation and skin histology. Our results demonstrate that simple housing modifications to reduce litter size, facilitate food access, and enhance environmental enrichment, can have a positive effect on the welfare of fragile animal models without interfering with the main characteristics of the phenotype.