Creatine Transporter (CrT; Slc6a8) Knockout Mice as a Model of Human CrT Deficiency

Mutations in the creatine (Cr) transporter (CrT; Slc6a8) gene lead to absence of brain Cr and intellectual disabilities, loss of speech, and behavioral abnormalities. To date, no mouse model of CrT deficiency exists in which to understand and develop treatments for this condition. The purpose of this study was to generate a mouse model of human CrT deficiency. We created mice with exons 2–4 of Slc6a8 flanked by loxP sites and crossed these to Cre:CMV mice to create a line of ubiquitous CrT knockout expressing mice. Mice were tested for learning and memory deficits and assayed for Cr and neurotransmitter levels. Male CrT−/y (affected) mice lack Cr in the brain and muscle with significant reductions of Cr in other tissues including heart and testes. CrT−/y mice showed increased path length during acquisition and reversal learning in the Morris water maze. During probe trials, CrT−/y mice showed increased average distance from the platform site. CrT−/y mice showed reduced novel object recognition and conditioned fear memory compared to CrT+/y. CrT−/y mice had increased serotonin and 5-hydroxyindole acetic acid in the hippocampus and prefrontal cortex. Ubiquitous CrT knockout mice have learning and memory deficits resembling human CrT deficiency and this model should be useful in understanding this disorder

Recognizing and Moving on from a Failed Paradigm: The Case of Agricultural Landscapes in Anglo-Saxon England c. AD 400–800

A central preoccupation for archaeologists is how and why material culture changes. One of the most intractable examples of this problem can be found between AD 400 and 800 in the enigmatic transformation of sub-Roman into Anglo-Saxon England. That example lies at the heart of this review, explored through the case of the agricultural economy. Although the ideas critically examined below relate specifically to early medieval England, they represent themes of universal interest: the role of migration in the transformation of material culture, politics, and economy in a post-imperial world, the significance of ‘‘core’’ and ‘‘periphery’’ in evolving polities, ethnogenesis as a strategy in kingdom building, property rights as a lens for investigating cultural change, and the relationship between hierarchical political structures and collective forms of governance. The first part of my argument proposes a structured response to paradigmatic stalemate by identifying and testing each underlying assumption, premise, and interpretative framework. The recognition of any fallacies, false premises, and flawed arguments might assist with an overall evaluation of the continuing utility of a discourse—whether it has life in it yet, or should be set aside. In either case, the recognition of its structure should enable arguments to be developed that do not lead into a disciplinary cul-de-sac, prevented by the orthodoxy from exploring new avenues for research. In the second part of the review, I deliberately adopt a starting point outside the limits of the current discourse. Freed from the confines of the conventional consensus, I experiment with an alternative ‘‘bottom-up’’ approach to change in early medieval England that contrasts with conventional ‘‘top-down’’ arguments. I focus in particular on how rights over agricultural property—especially collective rights—and the forms of governance implied by them may assist in illuminating the roles of tradition and transformation in effecting cultural change.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s10814-015-9088-