Current understanding of the functional roles of individual dopamine D1-like [D1, D5] and D2-like [D2L/s, D3, D4] receptor subtypes remains incomplete. In particular, the lack of pharmacological agonists and antagonists able to distinguish between D1 and D5 receptors means that any differential roles in the regulation of behavior are poorly understood. Mutant mice with targeted gene deletion ("knockout") of individual dopamine receptor subtypes offer an important alternative approach to resolving these functional roles. In congenic D1 mutants examined ethologically, progressive increases in specific topographies of behavior over wildtypes were considerably greater than those in D1 mutants on a mixed genetic background; D1 knockout appears to influence the neuronal substrate(s) of habituation to disrupt sculpture of the changing topography of behavior from initial exploration through to quiescence. Similarly, the D1 receptor appears to regulate specific topographies of orofacial movement in the mouse as these are "sculpted" in a time-dependent manner. Although the well-recognized role of the D1-like family in regulating several aspects of behavioral topography has been assumed to involve primarily D1 receptors, this presumption may require modification to accommodate a subtle but not negligible role for their D5 counterparts as evidenced in the phenotype of congenic D5 mutants.
Genetic background is a strong driver of phenotype, and when analyzing a mutant phenotype, it is critical that a genetically comparable wildtype stock is used as a control. Many of the meiotic mutants were isolated in EMS screens or created by P-element mutagenesis and do not have a congenic or isogenic wildtype control. We show here that the stock, commonly used for transgenesis in , shows significantly higher meiotic crossover rates, and there is likely a modifier of meiosis or germline development in the genetic background of this popular stock.
Nonketotic hyperglycinemia due to deficient glycine cleavage enzyme activity causes a severe neonatal epileptic encephalopathy. Current therapies based on mitigating glycine excess have only limited impact. An animal model with postnatal phenotyping is needed to explore new therapeutic approaches.
Cryptococcus neoformans is an opportunistic human fungal pathogen capable of surviving in a wide range of environments and hosts. It has been developed as a model organism to study fungal pathogenesis due to its fully sequenced haploid genome and optimized gene deletion and mutagenesis protocols. These methods have greatly aided in determining the relationship between Cryptococcus genotype and phenotype.
Unlabelled: Nonketotic hyperglycinemia due to deficient glycine cleavage enzyme activity causes a severe neonatal epileptic encephalopathy. Current therapies based on mitigating glycine excess have only limited impact. An animal model with postnatal phenotyping is needed to explore new therapeutic approaches.
Neuromuscular Immunopathology Research Laboratory, Division of Neuromuscular Disease, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address:
Mouse models are invaluable to understanding fundamental mechanisms in vascular biology during development, in health and different disease states. Several constitutive or inducible models that selectively knockout or knock in genes in vascular endothelial cells exist; however, functional and phenotypic differences exist between microvascular and macrovascular endothelial cells in different organs. In order to study microvascular endothelial cell-specific biological processes, we developed a Tamoxifen-inducible von Willebrand Factor (vWF) Cre recombinase mouse in the SJL background.
