Characterization of the Bex gene family in humans, mice, and rats

• Published in: Gene Vol. 357; no. 1; pp. 18 - 28
• Main Authors: Alvarez, Enrique, Zhou, Wenbo, Witta, Samir E., Freed, Curt R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 29-08-2005
• Subjects: Animals; Base Sequence; Brain - embryology; Cell Nucleus - metabolism; Chromosomes, Human, X - genetics; Cytoplasm - metabolism; Dopamine - metabolism; Expression array; Gene Expression Profiling - methods; Gene Expression Regulation, Developmental - physiology; Haplorhini; Heart - physiology; Humans; Liver - embryology; Mice; Molecular Sequence Data; Multigene Family - genetics; Muscle, Skeletal - metabolism; NADE; Nerve Tissue Proteins - genetics; Neurons - metabolism; Oligonucleotide Array Sequence Analysis - methods; Organ Specificity; pHGR74; Proteasome Endopeptidase Complex - metabolism; Rats; Rex3; Sequence Homology, Nucleic Acid; Species Specificity; Spinal Cord - embryology; Subtractive hybridization; Ventral mesencephalon; PBS; ORF; EST; PSI; Rex3; AN; HEK; GFP; NADE; Bex; hMTEA3; Expression array; IRES; Subtractive hybridization; pHGR74; NCBI; Ventral mesencephalon; PCR
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2005.05.012

To better understand the development of ventral mesencephalic dopamine neurons, we performed subtractive hybridization screens to find ventral mesencephalic genes expressed at rat embryonic day 10 when these neurons begin to differentiate. The most commonly identified genes in these screens were members of the Bex (Brain expressed X-linked) gene family, rat
Bex1 (
Rex3), and a novel gene, rat
Bex4. After identifying these genes, we then sought to characterize the Bex gene family. Two additional novel Bex genes (human
Bex5 and mouse
Bex6) were discovered through genomic databases.
Bex5 is present in humans and monkeys, but not rodents, while
Bex6 exists in mice, but not humans.
Bex4 and
Bex5 are localized to the X chromosome, are expressed in brain, and are similar in sequence.
Bex4 and
Bex5 are 54% and 56% identical to human
Bex3 (
pHGR74,
NADE). Mouse
Bex6 is on chromosome 16 and is 67% identical to mouse
Bex4. Human Bex gene expression was studied with tissue expression arrays probed with specific oligonucleotides. Human
Bex1 and
Bex2 have similar expression patterns in the central nervous system with high levels in pituitary, cerebellum, and temporal lobe, and
Bex1 is widely expressed outside of the central nervous system with high expression in the liver. Human
Bex4 is highly expressed in heart, skeletal muscle, and liver, while
Bex3 and
Bex5 are more widely expressed. The subcellular localization of the Bex proteins varies from nuclear (rat Bex1) to cytoplasmic (rat Bex3, human Bex5, and mouse Bex6) and to both nuclear and cytoplasmic (rat Bex2 and rat Bex4). Rat Bex3, rat Bex4, human Bex5, and mouse Bex6 are degraded by the proteasome, while rat Bex1 or Bex2 are not. Rat Bex3 protein can likely bind transition metals through a histidine-rich domain. Because this gene family was originally named Bex and because these genes are unified by sequence similarity and gene structure, we believe the Bex nomenclature should prevail over nomenclature based on function (NADE) that has not been extended to the other Bex genes. We conclude that the Bex gene family members are highly homologous but differ in their expression patterns, subcellular localization, and degradation by the proteasome.