Leiden Muscular Dystrophy pages

Dystrobrevin beta (DTNB)

(last modified October 14, 2002)



Contents




Summary


The mammalian dystrobrevin genes encode several protein isoforms that are expressed in different tissues, including brain and muscle. Blake et al. designated the isoform expressed in muscle as alpha-dystrobrevin and used the designation beta-dystrobrevin for the dystrophin-related protein they found to be abundantly expressed in brain and other tissues but not in muscle.

The human dystrobrevin beta (Gene Symbol DTNB [Blake]) gene was discovered through its similarity to dystrobrevin alpha. Peters et al. ( J. Biol.Chem. 272: 31561-31569, 1997) first described beta-dystrobrevin, derived from cDNAs cloned from human liver libraries. The DTNB gene was mapped to human 2p23-p22, a region syntenic with the most proximal 15 cM of mouse chromosome 12. The murine Dtnb gene contains 21 exons spanning over 130 kb of DNA. In common with dystrophin, beta-dystrobrevin is found in neurons of the cortex and hippocampal formation, but it is not found in the brain microvasculature. In the brain, beta-dystrobrevin co-precipitates with the dystrophin isoforms Dp71 and Dp140.

Yoshida et al. found that the N-terminal half of dystrobrevin participates in an association with the sarcoglycan-sarcospan complex. The authors hypothesized that the sarcoglycan-sarcospan complex is linked to the signaling protein neuronal nitric oxide synthase via alpha-syntrophin associated with dystrobrevin.

Blake found that the composition of the dystrophin-associated protein complex in the brain differs from that in muscle. Because beta-dystrobrevin and dystrophin are expressed in similar populations of neurons in the hippocampus and cortex, it is possible that beta-dystrobrevin interacts directly with dystrophin. If this is the case, then beta-dystrobrevin levels may be reduced in DMD patients similar to the reduction in sarcolemmal staining seen with other components of the DGC in dystrophic muscle. The findings may be relevant to the cognitive dysfunction affecting DMD/BMD patients.


The dystrobrevin beta gene


Links to other databases:
Gene Symbol nomenclature   LocusLink   OMIM Gene Map    GDB

The human dystrobrevin beta (Gene Symbol DTNB [Blake]) gene was discovered through its similarity to dystrobrevin alpha. Peters et al. ( J. Biol.Chem. 272: 31561-31569, 1997) first described beta-dystrobrevin, derived from cDNAs cloned from human liver libraries. By fluorescence in situ hybridization, Peters mapped the beta dystrobrevin gene to human 2p23-p22, a region syntenic with the most proximal 15 cM of mouse chromosome 12. Loh et al. assigned the mouse Dtnb gene to chromosome 12 by backcross mapping and showed that it contains 21 exons spanning over 130 kb of DNA. Beta-dystrobrevin is encoded by a 2.5-kb alternatively spliced transcript that is found throughout the brain. The main transcript encodes a 627-amino acid polypeptide with a predicted molecular weight of 71 kD.

Exon Exon size (bp) Intron size (kb) 5' cDNA position Splice after Remarks
1         5'UTR / .. bp coding
2          
3          
4          
5          
6          
7          
8          
9          
10          
11          
12          
13          
14          
15          
16          
17          
18          
19          
20          
21          

Legend:
Exon: numbering of exons and intron/exon boundaries are according to ..., with the first base of the Met-codon counted as position 1 (see ...Reference sequence). Exon size: size of exon indicated in basepairs. Intron size: size of intron indicated in kilobasepairs. 5' cDNA position: first base of the exon (according to cDNA sequence ...). Splice after: splicing occurs in between of two coding triplets (0), after the first (1) or the second (2) base of a triplet. Remarks: 5'UTR = 5' untranslated region, 3"UTR = 3' untranslated region. aamplification with primers 5'-tatctccgtctctctgattgctcc-3' and 5'-ttgcggactctgttgccctcttgt-3' (...).

primers for DNA-amplification


The dystrobrevin RNA


Links to other databases:     GenBank: AF022728     UniGene: Hs.13451

Beta-dystrobrevin is encoded by a 2.5-kb alternatively spliced transcript that is found throughout the brain. The main transcript encodes a 627-amino acid polypeptide with a predicted molecular weight of 71 kD.

primers for RNA-amplification


The dystrobrevin protein


Links to other databases:   GenBank: AAC05082

In common with dystrophin, beta-dystrobrevin is found in neurons of the cortex and hippocampal formation, but it is not found in the brain microvasculature. In the brain, beta-dystrobrevin coprecipitates with the dystrophin isoforms Dp71 and Dp140.

Blake found that the composition of the dystrophin-associated protein complex in the brain differs from that in muscle. Because beta-dystrobrevin and dystrophin are expressed in similar populations of neurons in the hippocampus and cortex, it is possible that beta-dystrobrevin interacts directly with dystrophin. If this is the case, then beta-dystrobrevin levels may be reduced in DMD patients similar to the reduction in sarcolemmal staining seen with other components of the DGC in dystrophic muscle. The findings may be relevant to the cognitive dysfunction affecting DMD/BMD patients.

dystrobevin-beta antibodies

Similarity to other proteins

Human dystrobrevin beta shows ... similarity / ... identity (amino acid level) to dystrobrevin alpha.


Dystrobrevin and disease


Links to other databases:   OMIM: 602415

No reports have yet associated mutations in the utrophin gene with disease.

Animal models


Miscellaneous


DNA-primers:

Amplified Length Reference forward primer reverse primer Name
exon 1          

Legend:
Exonic sequences are in upper case, intronic and gene flanking sequences in lower case and added primer tails in italics. Amplified: region amplified. Numbering of exons is according to .... Length: length of PCR-product in basepairs. Reference: publication describing the primer(s). Forward primer: sequence of forward primer. Reverse primer: sequence of reverse primer. Name: name of the primers.


RNA-primers:

Amplified Length Reference Forward primer Reverse primer Name
           

Legend:
Exonic sequences are in upper case, intronic and gene flanking sequences in lower case and added primer tails in italics. Amplified: region amplified. Numbering of exons is according to .... Length: length of PCR-product in basepairs. Reference: publication describing the primer(s). Forward primer: sequence of forward primer. Reverse primer: sequence of reverse primer. Name: name of the primers.


Dystrobrevin sequences



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