Mouse behavioral mutants have neuroimaging abnormalities

Abstract

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. Hum Brain Mapp 28: [567][568][569][570][571][572][573][574][575] 2007. V V C 2007 Wiley-Liss, Inc.

Regionally reduced brain volume, altered serotonin neurochemistry, and abnormal behavior in mice null for the circadian rhythm output gene Magel2

“…In a recent study of mice with heritable mutations that display behavioral symptoms, 87% of these strains showed neuroimaging abnormalities including volumetric changes using high resolution MRI [Nieman et al, 2007]. In keeping with this finding, Magel2-null mice have brain abnormalities that we detected by MRI.…”

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

“…Had those studies been performed on the same animals, that is, behavioral testing of the animals with either in vivo imaging concurrently and/or ex vivo imaging after sacrifice, it is likely that there would be even more consistency. In a previous report, both behavioral and neuroanatomical phenotypic outcomes were detected in 17 of 19 different mouse models [155]. To build upon this further, it has been shown that behavioral training can directly influence the neuroanatomy.…”

White and Gray Matter Abnormalities After Cranial Radiation in Children and Mice

“…Radiation treatment in mice also results in behavioral abnormalities, including impaired learning and memory that has been associated with reduced hippocampal neurogenesis (17)(18)(19). As may be expected (20,21), anatomical changes through development are also present (22) with a dependence on age, dose, and sex (23), reminiscent of known risk factors in human patients (9,24).…”