Mouse behavioral mutants have neuroimaging abnormalities.
Impaired cognitive, memory, or motor performance is a distinguishing characteristic of neurological diseases. Although these symptoms are frequently the most evident in human patients, additional markers of disease are critical for proper diagnosis and staging. Noninvasive neuroimaging methods have become essential in this capacity and provide means of evaluating disease and tracking progression. These imaging methods are also becoming available to scientists in the research laboratory for assessment of animal models of neurological disease. Imaging in mouse models of neurological disease is of particular interest, owing to the availability of inbred strains and genetic manipulation tools that permit detailed investigation of the roles of various genes and gene products in disease pathogenesis. However, the relative prevalence of neuroimaging abnormalities in mice exhibiting neurological symptoms has not been reported. This prevalence has both theoretical and practical value because it is influenced by both the sensitivity of macroscopic anatomical measures to underlying genetic and disease processes and by the efficiency of neuroimaging in detecting and characterizing these effects. In this paper, we describe a meta-analysis of studies involving behavioral mouse mutants at our laboratory. In summary, we have evaluated 15 different mutant genotypes, of which 13 showed abnormal neuroimaging findings. This indicates a surprisingly high prevalence of neuroimaging abnormalities (87%) and suggests that disease processes affecting behavior generally alter neuroanatomy as well. As a consequence, neuroimaging provides a highly sensitive marker of neurological disease in mice exhibiting abnormal behavior.
Nieman
Brian J
BJ
Mouse Imaging Centre, Hospital for Sick Children, Toronto, Canada.
Lerch
Jason P
JP
Bock
Nicholas A
NA
Chen
X Josette
XJ
Sled
John G
JG
Henkelman
R Mark
RM
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000002:abnormalities* / Q000473:pathology*; D001931:Brain Mapping; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D005824:Genetics, Behavioral; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains