Transgenic and knock‐out mouse pups: the growing need for behavioral analysis

Abstract

Few laboratories working with transgenic and knockout mice analyze the neurobehavioral consequences of genetic manipulation in early ontogeny. However, the study of behavioral endpoints during the early postnatal period in genetically modified mice is important not only to assess possible developmental abnormalities, but also to better understand and disentangle the effects of genetic manipulations in adulthood. We propose that the assessment of neurobehavioral development represents an appropriate strategy to identify possible compensatory and/or unexpected effects. Nowadays, a large number of experimental protocols that take into account the practical constraints imposed by the peculiar physiological and behavioral responses of an immature subject are available to assess the neurobehavioral profile of developing mice. While this knowledge should be applied to the field of transgenic and knock-out mice in general, it should be recommended, in particular, for the study of mouse models of neurodevelopmental disorders.

Advances in behavioral genetics: mouse models of autism

“…[31][32][33] Wagner and colleagues 34,35 investigated abnormalities in neonatal and juvenile mice relevant to neurodevelopmental disorders using sets of behavioral tasks for sensorimotor abilities, learning and memory, and other functional domains. The researchers utilized a test for juvenile play to reveal reduced social interaction in a genetic model for autism, the Engrailed 2 null mouse.…”

Early Behavioural Alterations in Mouse Models of Autism Spectrum Disorders: A Step Forward Towards the Discovery of New Therapeutic Approaches

“…Keeping in mind Pat Bateson's cardinal view of neurobehavioural development in mammals, as a process akin to the metamorphosis of a caterpillar into a butterfly, we can investigate appropriate behavioural endpoints for each selected maturational step, and use standardized methodological procedures to assess sensory-motor, emotional and cognitive domains in developing mice. However, this knowledge is rarely exploited by neurobiologists working with transgenic and knock-out mice (Branchi & Ricceri, 2002). To date such studies are primarily focused on adult phenotyping and neglect the crucial information provided by the study of ontogeny.…”

“…Moreover, in transgenic and knockout mice, developmental analysis can shed light on gene effects not accessible when studying adulthood alone. Behavioural testing during ontogeny can help our understanding of how a genetic manipulation affects central nervous system function in ontogeny and it can represent an appropriate strategy to identify possible compensatory and/or unexpected effects (Branchi & Ricceri, 2002). Since the development of different neural systems is differentially timed, the ontogenetic analysis of associated behavioural phenotypes can, for instance, represents a powerful strategy to investigate the effects of genetic manipulations on different brain functions before the occurrence of possible compensatory events.…”

“…Time of onset of selected somatic changes and the time of first appearance of various reflexes and behavioural patterns show a remarkable regularity, providing an effective tool to assess possible neurobehavioural/developmental alterations (Bignami, 1996). Particularly in models of neurodevelopmental disorders, it seems therefore critical to conduct behavioural phenotyping during the developmental period (Branchi & Ricceri, 2002;De Filippis et al, 2010a). As well as defining an Alzheimer animal model via its behavioural characterization only in the pre-weaning phase could be at least considered hazardous, it is similarly limiting and inappropriate to describe adult, but not infant or adolescent behaviour in animal models of neurological disorders such as autism with an early onset and developmental pathology.…”

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

“…With this increased popularity in experimental models, the interest in developing sensitive behavioral assessments of functional outcome following injury has also increased [1][2][3][4][5][6][7] . The development of animal training protocols that mimic both rehabilitation and compensatory strategies used by human stroke survivors improves the ability to successfully translate findings from experimental animal studies to use in the clinic 8 .…”