Systematic phenotyping of genetically modified animals is an essential aspect of analyzing pleiotropic effects of genes. Irmler et al. use such a screen in a reporter mouse line for impaired protein quality control associated with Alzheimer’s disease. Unexpected respiratory dysfunction was found that apparently is mediated by mouse brainstem nuclei where a dysfunctional ubiquitin protein (UBB+1) accumulates (left). In patients with Alzheimer’s disease similar brainstem nuclei also accumulate the mutant protein (right: lateral parabrachial nucleus) suggesting a similar role. Respiratory function should therefore be considered by clinicians when diagnosing patients with mild cognitive impairment.
Irmler et al., Long-term proteasomal inhibition in transgenic mice by UBB(+1) expression results in dysfunction of central respiration control reminiscent of brainstem neuropathology in Alzheimer patients, Acta Neuropathol, DOI 10.1007/s00401-012-1003-7