Disease relevance of Pou3f4

• The presence of vector DNA in the brain 4 months after transplantation suggests a role for gene transfer and stem cell transplantation in the treatment strategies for metachromatic leukodystrophy [1].

High impact information on Pou3f4

• Neurons comprising the endocrine hypothalamus are disposed in several nuclei that develop in tandem with their ultimate target the pituitary gland, and arise from a primordium in which three related class III POU domain factors, Brn-2, Brn-4, and Brn-1, are initially coexpressed [2].
• Recently, pilot mapping experiments suggested that the mouse Brn4 / Pou3f4 gene co-segregated with the slf locus on the mouse X chromosome [3].
• This inversion selectively eliminates the expression of the Brn4 gene in the developing inner ear, but not the neural tube [3].
• The sex-linked fidget mutation abolishes Brn4/Pou3f4 gene expression in the embryonic inner ear [3].
• These mapping data, in conjunction with the observation that the vertical head-shaking phenotype of slf mutants is identical to that observed in mice with a targeted deletion of the Brn4 gene, suggested that slf is a mutant allele of the Brn4 gene [3].

Biological context of Pou3f4

• Mutagenesis of the POU-domain gene Brn4/Pou3f4 causes defects in the cochlear duct, semicircular canal, temporal bone and stapes footplate [4].
• Brain-4 (Brn-4) is expressed in the pancreatic anlaga of the mouse foregut at e10 in the alpha cells and transactivates glucagon gene expression [5].
• We expressed Brn-4 in pancreatic precursors or beta cell lineage in transgenic mice by placing it under either Idx-1 or insulin promoter (rat insulin II promoter) control, respectively [5].
• From a cDNA library prepared from fetal muscle mRNA, we cloned a cDNA identical to that of Brn-4, a POU class II gene previously cloned from neural tissues [6].
• In this paper, we have identified the nature of the slf mutation, and demonstrated that it is an X chromosomal inversion with one breakpoint close to Brn4 [3].

Anatomical context of Pou3f4

• Targeted mutagenesis of the POU-domain gene Brn4/Pou3f4 causes developmental defects in the inner ear [7].
• Misexpression of Brn-4 by the Idx-1 promoter results in ectopic expression of the proglucagon gene in insulin-expressing pancreatic beta cells, whereas misexpression by rat insulin II promoter did not [5].
• These results indicated that mutation of the POU-domain gene, Brn4, changed middle-ear sound conduction when measured at the umbo [4].
• Regulatory regions from the Brn4 promoter direct LACZ expression to the developing forebrain and neural tube [8].
• The presence of this pathology, the mid-frequency loss in incus sensitivity and the variability in incus velocity among animals suggested that abnormal stapes behavior in Brn4 deficient mice may determine the response of the ossicles, and thus account for the abnormal mid-frequency umbo behavior seen in knockout animals [4].

Associations of Pou3f4 with chemical compounds

• In the rat, Brn-4 is expressed in 76 and 65% of vasopressin neurons in the paraventricular and supraoptic nuclei, respectively; but in only 10% of corticotropin-releasing factor neurons in the paraventricular nucleus of the hypothalamus [9].
• The immunoreactivities of p38alpha and p38beta MAPKs were markedly increased in the brain 4 days after KA administration, especially in the areas undergoing selective neuronal loss [10].

Regulatory relationships of Pou3f4

• In contrast, the regulation of Brn4 which is also expressed in the SON and PVN is independent of Otp function [11].

Other interactions of Pou3f4

• Thus, in contrast to controls, alpha-cells of mutant mice had protracted expression of Nkx 6.1 and Pdx-1, but did not express Brn-4 [12].
• The early developmental expression of Brn-4 appears to be a dominant regulator of the glucagon expressing alpha cell lineage, even in the context of the beta cell lineage [5].
• The mRNAs of two additional POU genes, Emb (POU class VI) and Oct-1 (POU class II), were also expressed in developing muscle and, unlike Brn-4, continued to be expressed in postnatal and adult muscles [6].
• Hence no strong evidence links Otp and Brn4 in the same regulatory pathway [11].
• Cdx-2 and Brn-4 are recognized as transcriptional activators for the proglucagon gene [13].

Analytical, diagnostic and therapeutic context of Pou3f4

• Quantitative real-time polymerase chain reaction (PCR) of genomic DNA for the EGFP gene showed that more fetal cells were present in the maternal brain 4 weeks postpartum than on the day of parturition [14].
• RESULTS: A dysmorphic constriction of the superior arc of the SSCC in Brn4 knockout mice was initially detectable at P14 [15].

References