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Title: The human peripheral benzodiazepine receptor gene: Cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasia

Abstract

The mitochondrial benzodiazepine receptor (mBzR) appears to be a key factor in the flow of cholesterol into mitochondia to permit the initiation of steroid hormone synthesis. The mBzR consists of three components; the 18-kDa component on the outer mitochondrial membrane appears to contain the benzodiazepine binding site, and is hence often termed the peripheral benzodiazepine receptor (PBR). Using a cloned human PBR cDNA as probe, the authors have cloned the human PBR gene. The 13-kb gene is divided into four exons, with exon 1 encoding only a short 5[prime] untranslated segment. The 5[prime] flanking DNA lacks TATA and CAAT boxes but contains a cluster of SP-1 binding sites, typical of [open quotes]housekeeping[close quotes] genes. The encoded PBR mRNA is alternately spliced into two forms: [open quotes]authentic[close quotes] PBR mRNA retains all four exons, while a short form termed PBR-S lacks exon 2. While PBR-S contains a 102-codon open reading frame with a typical initiator sequence, the reading frame differs from that of PBR, so that the encoded protein is unrelated to PBR. RT-PCR and RNase protection experiments confirm that both PBR and PBR-S are expressed in all tissues examined and that expression of PBR-S is about 10 times the levelmore » of PBR. Expression of PBR cDNA in pCMV5 vectors transfected into COS-1 cells resulted in increased binding of [[sup 3]H]PK11195, but expression of PBR-S did not. It has been speculated that patients with congenital lipoid adrenal hyperplasia, who cannot make any steroids, might have a genetic lesion in mBzR. RT-PCR analysis of testicular RNA from such a patient, sequencing of the cDNA, and blotting analysis of genomic DNA all indicate that the gene and mRNA for the PBR component of mBzR are normal in this disease. 36 refs., 6 figs.« less

Authors:
;  [1]; ;  [2]
  1. Univ. of California, San Francisco, CA (United States)
  2. Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)
Publication Date:
OSTI Identifier:
6975691
Resource Type:
Journal Article
Journal Name:
Genomics; (United States)
Additional Journal Information:
Journal Volume: 18:3; Journal ID: ISSN 0888-7543
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ADRENAL GLANDS; METABOLIC DISEASES; GENES; DNA SEQUENCING; DNA-CLONING; MITOCHONDRIA; BIOLOGICAL PATHWAYS; RECEPTORS; STEROIDS; BIOSYNTHESIS; BODY; CELL CONSTITUENTS; CLONING; DISEASES; DNA HYBRIDIZATION; ENDOCRINE GLANDS; GLANDS; HYBRIDIZATION; MEMBRANE PROTEINS; ORGANIC COMPOUNDS; ORGANS; PROTEINS; STRUCTURAL CHEMICAL ANALYSIS; SYNTHESIS; 550400* - Genetics

Citation Formats

Lin, D, Miller, W L, Chang, Y J, and Strauss, III, J F. The human peripheral benzodiazepine receptor gene: Cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasia. United States: N. p., 1993. Web. doi:10.1016/S0888-7543(05)80367-2.
Lin, D, Miller, W L, Chang, Y J, & Strauss, III, J F. The human peripheral benzodiazepine receptor gene: Cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasia. United States. https://doi.org/10.1016/S0888-7543(05)80367-2
Lin, D, Miller, W L, Chang, Y J, and Strauss, III, J F. 1993. "The human peripheral benzodiazepine receptor gene: Cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasia". United States. https://doi.org/10.1016/S0888-7543(05)80367-2.
@article{osti_6975691,
title = {The human peripheral benzodiazepine receptor gene: Cloning and characterization of alternative splicing in normal tissues and in a patient with congenital lipoid adrenal hyperplasia},
author = {Lin, D and Miller, W L and Chang, Y J and Strauss, III, J F},
abstractNote = {The mitochondrial benzodiazepine receptor (mBzR) appears to be a key factor in the flow of cholesterol into mitochondia to permit the initiation of steroid hormone synthesis. The mBzR consists of three components; the 18-kDa component on the outer mitochondrial membrane appears to contain the benzodiazepine binding site, and is hence often termed the peripheral benzodiazepine receptor (PBR). Using a cloned human PBR cDNA as probe, the authors have cloned the human PBR gene. The 13-kb gene is divided into four exons, with exon 1 encoding only a short 5[prime] untranslated segment. The 5[prime] flanking DNA lacks TATA and CAAT boxes but contains a cluster of SP-1 binding sites, typical of [open quotes]housekeeping[close quotes] genes. The encoded PBR mRNA is alternately spliced into two forms: [open quotes]authentic[close quotes] PBR mRNA retains all four exons, while a short form termed PBR-S lacks exon 2. While PBR-S contains a 102-codon open reading frame with a typical initiator sequence, the reading frame differs from that of PBR, so that the encoded protein is unrelated to PBR. RT-PCR and RNase protection experiments confirm that both PBR and PBR-S are expressed in all tissues examined and that expression of PBR-S is about 10 times the level of PBR. Expression of PBR cDNA in pCMV5 vectors transfected into COS-1 cells resulted in increased binding of [[sup 3]H]PK11195, but expression of PBR-S did not. It has been speculated that patients with congenital lipoid adrenal hyperplasia, who cannot make any steroids, might have a genetic lesion in mBzR. RT-PCR analysis of testicular RNA from such a patient, sequencing of the cDNA, and blotting analysis of genomic DNA all indicate that the gene and mRNA for the PBR component of mBzR are normal in this disease. 36 refs., 6 figs.},
doi = {10.1016/S0888-7543(05)80367-2},
url = {https://www.osti.gov/biblio/6975691}, journal = {Genomics; (United States)},
issn = {0888-7543},
number = ,
volume = 18:3,
place = {United States},
year = {Wed Dec 01 00:00:00 EST 1993},
month = {Wed Dec 01 00:00:00 EST 1993}
}