Male Akita mice develop signs of bladder underactivity independent of NLRP3 as a result of a decrease in neurotransmitter release from efferent neurons.

Diabetic bladder dysfunction (DBD) is a prevalent diabetic complication that is recalcitrant to glucose control. Using the Akita mouse model (type 1) bred to be NLR family pyrin domain containing 3 (NLRP3) or NLRP3, we have previously found that females (mild hyperglycemia) progress from an overactive to underactive bladder phenotype and that this progression was dependent on NLRP3-induced inflammation. Here, we examined DBD in the male Akita mouse (severe hyperglycemia) and found by urodynamics only a compensated underactive-like phenotype (increased void volume and decreased frequency but unchanged efficiency).

The regional pattern of D4 gene expression in human brain.

Using a competitive reverse transcription-polymerase chain reaction (RT-PCR) assay levels of D4 gene expression have been determined in 16 regions obtained from a single control brain. Relatively high levels of expression were detected in the prefrontal and temporolimbic structures whilst low levels were detected in striatal regions. This pattern correlates with the reported distribution of the D4 receptor.

No difference in the expression of the D4 gene in post-mortem frontal cortex from controls and schizophrenics.

The primary biochemical theory of schizophrenia has centered on the role of dopaminergic dysfunction in the illness. The D2 receptor has been primarily indicated however, some atypical neuroleptics may not act at D2. The D4 receptor has a high affinity for the atypical antipsychotic clozapine and is therefore a potential target for drug design.

Genetic linkage analysis of schizophrenia using chromosome 11q13-24 markers in Israeli pedigrees.

It is generally agreed that there is a genetic component in the etiology of schizophrenia which may be tested by the application of linkage analysis to multiply-affected families. One genetic region of interest is the long arm of chromosome 11 because of previously reported associations of genetic variation in this region with schizophrenia, and because of the fact that it contains the locus for the dopamine D2 receptor gene. In this study we have examined the segregation of schizophrenia with microsatellite dinucleotide repeat DNA markers along chromosome 11q in 5 Israeli families multiply-affected for schizophrenia.

A study of altered gene expression in frontal cortex from schizophrenic patients using differential screening.

In order to examine the molecular basis of schizophrenia we have employed a sequential differential hybridisation protocol to isolate mRNAs whose abundances are altered in schizophrenic compared to normal frontal cortex. Five cDNAs present at abnormal levels in the schizophrenic brain have been isolated by this method. The sequences were identified on the basis of homologies in the EMBL and Genbank databases.