Homozygous mutation in leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway-Mowat syndrome.

Background: Microcephaly with nephrotic syndrome is a rare co-occurrence, constituting the Galloway-Mowat syndrome (GAMOS), caused by mutations in (OMIM: 616144). However, not all patients harbour demonstrable deleterious variants, suggesting that there are other yet unidentified factors contributing to GAMOS aetiology.

Methods: Autozygosity mapping and candidate analysis was used to identify deleterious variants in consanguineous families.

Cocaine-conditioned place preference by dopamine-deficient mice is mediated by serotonin.

Rodents learn to associate the rewarding effects of drugs with the environment in which they are encountered and, subsequently, will display a conditioned place preference (CPP) for that environment. Cocaine-induced CPP is generally thought to be mediated through inhibition of the dopamine transporter and the consequent increase in extracellular dopamine. However, here we report that dopamine-deficient (DD) mice formed a CPP for cocaine that was not blocked by a dopamine D1-receptor antagonist.

Genetic disruption of dopamine production results in pituitary adenomas and severe prolactinemia.

Background: Dopamine release from tuberoinfundibular dopamine neurons into the median eminence activates dopamine-D2 receptors in the pituitary gland where it inhibits lactotroph function.

Methods: We have previously described genetic dopamine-deficient mouse models which lack the ability to synthesize dopamine. Because these animals require daily treatment with 3,4-L-dihydroxyphenylalanine (L-dopa) to survive, it has not been possible to examine the consequences of chronic loss of dopamine on pituitary physiology.

Local dopamine production in the dorsal striatum restores goal-directed behavior in dopamine-deficient mice.

To determine whether dopamine signaling in the dorsal striatum is sufficient for performance of goal-directed behaviors, local dopamine production was restored in the dorsal striatum of dopamine-deficient (DD) mice through viral-mediated gene therapy. Virally rescued DD (vrDD) mice were tested for learning of an appetitive T-maze task designed to measure goal-directed behavior. The results indicate that in contrast with the performance of DD mice that have dysregulated dopamine signaling, vrDD mice were able to perform the T-maze task and reverse their behavior as well as sham-operated control mice.

Morphine reward in dopamine-deficient mice.

Dopamine has been widely implicated as a mediator of many of the behavioural responses to drugs of abuse. To test the hypothesis that dopamine is an essential mediator of various opiate-induced responses, we administered morphine to mice unable to synthesize dopamine. We found that dopamine-deficient mice are unable to mount a normal locomotor response to morphine, but a small dopamine-independent increase in locomotion remains.

Dysregulation of dopamine signaling in the dorsal striatum inhibits feeding.

Dopamine signaling is an important component of many goal-directed behaviors, such as feeding. Acute disruption of dopamine signaling using pharmacological agents tends to inhibit normal feeding behaviors in rodents. Likewise, genetically engineered dopamine-deficient (DD) mice are unable to initiate sufficient feeding and will starve by approximately 3 weeks of age if untreated.