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Genetics Home Reference: your guide to understanding genetic conditions
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MESP2

Reviewed February 2011

What is the official name of the MESP2 gene?

The official name of this gene is “mesoderm posterior basic helix-loop-helix transcription factor 2.”

MESP2 is the gene's official symbol. The MESP2 gene is also known by other names, listed below.

What is the normal function of the MESP2 gene?

The MESP2 gene provides instructions for making a transcription factor, which is a protein that attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The MESP2 protein controls the activity of genes in the Notch pathway, an important pathway in embryonic development. The Notch pathway plays a critical role in the development of vertebrae. Specifically, the MESP2 protein and the Notch pathway are involved in separating future vertebrae from one another during early development, a complex process called somite segmentation. Although the exact mechanism of somite segmentation is unclear, it appears to require the activity of several proteins in the Notch pathway, including the NOTCH1 protein and the MESP2 protein, to be turned on and off in a specific pattern (oscillate).

The MESP2 protein regulates Notch activity by turning on (activating) genes in the Notch pathway, which ultimately block (repress) the activity of the NOTCH1 protein. Additionally, through unknown mechanisms, the MESP2 protein seems to mark the boundary separating future vertebrae from one another.

Does the MESP2 gene share characteristics with other genes?

The MESP2 gene belongs to a family of genes called bHLH (basic helix-loop-helix).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the MESP2 gene related to health conditions?

spondylocostal dysostosis - caused by mutations in the MESP2 gene

At least one mutation in the MESP2 gene causes a rare type of spondylocostal dysostosis, called spondylocostal dysostosis type 2. This condition is characterized by abnormal development of bones in the spine and ribs. A duplication mutation in the MESP2 gene, in which four DNA nucleotides, ACCG, are repeated once (duplicated), has been found to cause spondylocostal dysostosis type 2. The mutation, which occurs at position 500 in the DNA sequence, is known as 500-503dup. The repeated DNA sequence creates an early stop signal in the instructions for making the MESP2 protein. The resulting protein is short (truncated) and does not fully function. Consequently, the NOTCH1 protein is constantly active and does not oscillate. The boundary separating future vertebrae does not form and somite segmentation does not occur properly. This results in the malformation and fusion of the bones of the spine and ribs seen in spondylocostal dysostosis type 2.

spondylothoracic dysostosis - caused by mutations in the MESP2 gene

At least three mutations in the MESP2 gene have been found to cause spondylothoracic dysostosis, a condition characterized by abnormal development of bones in the spine and ribs. All of the known mutations replace one protein building block (amino acid) in the protein sequence. The most common mutation replaces the amino acid glutamate with a premature stop signal at position 103 (written as Glu103Ter or E103X). A similar mutation occurs at amino acid position 230 (written as Glu230Ter or E230X). The third mutation replaces the amino acid leucine with the amino acid valine at position 125 (written as Leu125Val or L125V). Most affected individuals have the Glu103Ter mutation in both copies of the MESP2 gene. However, a few people with spondylothoracic dysostosis have the Glu103Ter mutation in one copy of the MESP2 gene and either the Leu125Val or the Glu230Ter mutation in the other copy.

Mutations in the MESP2 gene prevent the production of any protein or lead to the production of an abnormally short, nonfunctional protein. When the MESP2 protein is nonfunctional or absent, the NOTCH1 protein is abnormally active and the boundary separating future vertebrae from one another does not form. This results in the malformation and fusion of the bones of the spine and ribs seen in spondylothoracic dysostosis.

Where is the MESP2 gene located?

Cytogenetic Location: 15q26.1

Molecular Location on chromosome 15: base pairs 89,776,357 to 89,778,753

The MESP2 gene is located on the long (q) arm of chromosome 15 at position 26.1.

The MESP2 gene is located on the long (q) arm of chromosome 15 at position 26.1.

More precisely, the MESP2 gene is located from base pair 89,776,357 to base pair 89,778,753 on chromosome 15.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about MESP2?

You and your healthcare professional may find the following resources about MESP2 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the MESP2 gene or gene products?

  • bHLHc6
  • class C basic helix-loop-helix protein 6
  • mesoderm posterior 2 homolog (mouse)
  • mesoderm posterior protein 2
  • MESP2_HUMAN
  • SCDO2

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding MESP2?

amino acid ; class ; DNA ; duplication ; embryonic ; gene ; leucine ; malformation ; mesoderm ; mutation ; posterior ; protein ; protein sequence ; transcription ; transcription factor ; valine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Cornier AS, Staehling-Hampton K, Delventhal KM, Saga Y, Caubet JF, Sasaki N, Ellard S, Young E, Ramirez N, Carlo SE, Torres J, Emans JB, Turnpenny PD, Pourquié O. Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome. Am J Hum Genet. 2008 Jun;82(6):1334-41. doi: 10.1016/j.ajhg.2008.04.014. Epub 2008 May 15. (http://www.ncbi.nlm.nih.gov/pubmed/18485326?dopt=Abstract)
  • Ferjentsik Z, Hayashi S, Dale JK, Bessho Y, Herreman A, De Strooper B, del Monte G, de la Pompa JL, Maroto M. Notch is a critical component of the mouse somitogenesis oscillator and is essential for the formation of the somites. PLoS Genet. 2009 Sep;5(9):e1000662. doi: 10.1371/journal.pgen.1000662. Epub 2009 Sep 25. (http://www.ncbi.nlm.nih.gov/pubmed/19779553?dopt=Abstract)
  • Gene Review: Spondylocostal Dysostosis, Autosomal Recessive (http://www.ncbi.nlm.nih.gov/books/NBK8828)
  • Gene Review: Spondylothoracic Dysostosis (http://www.ncbi.nlm.nih.gov/books/NBK45316)
  • Gibb S, Maroto M, Dale JK. The segmentation clock mechanism moves up a notch. Trends Cell Biol. 2010 Oct;20(10):593-600. doi: 10.1016/j.tcb.2010.07.001. Epub 2010 Aug 18. Review. (http://www.ncbi.nlm.nih.gov/pubmed/20724159?dopt=Abstract)
  • Morimoto M, Takahashi Y, Endo M, Saga Y. The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity. Nature. 2005 May 19;435(7040):354-9. (http://www.ncbi.nlm.nih.gov/pubmed/15902259?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/145873)
  • Oginuma M, Takahashi Y, Kitajima S, Kiso M, Kanno J, Kimura A, Saga Y. The oscillation of Notch activation, but not its boundary, is required for somite border formation and rostral-caudal patterning within a somite. Development. 2010 May;137(9):1515-22. doi: 10.1242/dev.044545. Epub 2010 Mar 24. (http://www.ncbi.nlm.nih.gov/pubmed/20335362?dopt=Abstract)
  • Sasaki N, Kiso M, Kitagawa M, Saga Y. The repression of Notch signaling occurs via the destabilization of mastermind-like 1 by Mesp2 and is essential for somitogenesis. Development. 2011 Jan;138(1):55-64. doi: 10.1242/dev.055533. Epub 2010 Nov 23. (http://www.ncbi.nlm.nih.gov/pubmed/21098559?dopt=Abstract)
  • Sparrow DB, Chapman G, Turnpenny PD, Dunwoodie SL. Disruption of the somitic molecular clock causes abnormal vertebral segmentation. Birth Defects Res C Embryo Today. 2007 Jun;81(2):93-110. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17600782?dopt=Abstract)
  • Whittock NV, Sparrow DB, Wouters MA, Sillence D, Ellard S, Dunwoodie SL, Turnpenny PD. Mutated MESP2 causes spondylocostal dysostosis in humans. Am J Hum Genet. 2004 Jun;74(6):1249-54. Epub 2004 Apr 30. (http://www.ncbi.nlm.nih.gov/pubmed/15122512?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2011
Published: December 16, 2014