Incidental Mutation 'R0036:Eln'

• ID: 15645
• Institutional Source: Beutler Lab
• Gene Symbol: Eln
• Ensembl Gene: ENSMUSG00000029675
• Gene Name: elastin
• Synonyms: E030024M20Rik, tropoelastin
• MMRRC Submission: 038330-MU
• Essential gene?: Essential (E-score: 1.000)
• Stock #: R0036 (G1)
• Status: Validated
• Chromosome: 5
• Chromosomal Location: 134731447-134776177 bp(-) (GRCm39)
• Type of Mutation: critical splice donor site (2 bp from exon)
• DNA Base Change (assembly): A to G at 134739914 bp (GRCm39)
• Zygosity: Heterozygous
• Ref Sequence: ENSEMBL: ENSMUSP00000015138
• Gene Model: predicted gene model for transcript(s): [ENSMUST00000015138] [ENSMUST00000201856]
• AlphaFold: P54320
• Predicted Effect: probably null; Transcript: ENSMUST00000015138
• SMART Domains: Protein: ENSMUSP00000015138; Gene: ENSMUSG00000029675

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
low complexity region	183	220	N/A	INTRINSIC
low complexity region	224	264	N/A	INTRINSIC
low complexity region	292	301	N/A	INTRINSIC
low complexity region	312	446	N/A	INTRINSIC
low complexity region	451	798	N/A	INTRINSIC
low complexity region	818	849	N/A	INTRINSIC

• Predicted Effect: probably benign; Transcript: ENSMUST00000201856
• SMART Domains: Protein: ENSMUSP00000144555; Gene: ENSMUSG00000029675

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
low complexity region	183	220	N/A	INTRINSIC
SCOP:d1iq0a2	227	280	8e-3	SMART

• Predicted Effect: noncoding transcript; Transcript: ENSMUST00000202570
• Meta Mutation Damage Score: 0.9755
• Coding Region Coverage:
  • 1x: 79.1%
  • 3x: 69.3%
  • 10x: 43.3%
  • 20x: 23.5%
• Validation Efficiency: 91% (49/54)
• MGI Phenotype: FUNCTION: This gene encodes elastin, the extracellular matrix protein that forms a major structural component of several tissues including lungs and arterial walls. Cleavage of the signal peptide from the encoded precursor generates soluble tropoelastin which undergoes lysine-derived crosslinking to form elastin polymers. Mice lacking the encoded protein exhibit defective lung development, and die of an obstructive arterial disease resulting from subendothelial cell proliferation and reorganization of smooth muscle. [provided by RefSeq, Aug 2015] ; PHENOTYPE: Mice homozygous for null allele die in the early postnatal period of an obstructive arterial disease. They exhibit a decrease in arterial diameter due to subendothelial accumulation of arterial smooth muscle, and display defective terminal airway development resulting in emphysematous morphology. [provided by MGI curators]
• Allele List at MGI:

  All alleles(2) : Targeted(2)

• Posted On: 2012-12-21
• Science Writer: Anne Murray

Protein Function and Prediction

Elastin is a major component of elastic fibers in connective tissue (1) including the extracellular matrix of arteries (2), and in the alveoli of the lung (3). Elastin confers resilience upon structures that undergo repetitive physiologic stress (3;4).

Background

Table 1.  Human phenotypes associated with mutations associated with mutations in ELN.

Phenotype	OMIM #	Description	Refs
Autosomal dominant cutis laxa	123700	A collection of disorders that are typified by loose and/or wrinkled skin that imparts a prematurely aged appearance.	(5)
Supravalvar aortic stenosis	185500	Localized or diffuse narrowing of the ascending aorta; a frequent feature of Williams-Beuren syndrome	(6;7)
Williams-Beuren syndrome	194050	A syndrome characterized by supravalvular aortic stenosis, multiple peripheral pulmonary arterial stenoses, 'elfin face,' mental and statural deficiency, characteristic dental malformation, and infantile hypercalcemia	(8)

Eln^{tm1Dyl/tm1Dyl}; MGI:2153007

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Mice homozygous for null allele die in the early postnatal period of an obstructive arterial disease (2;3). They exhibit a decrease in arterial diameter due to subendothelial accumulation of arterial smooth muscle, and display defective terminal airway development resulting in emphysematous morphology (2).

References

  1. Uitto, J., Christiano, A. M., Kahari, V. M., Bashir, M. M., and Rosenbloom, J. (1991) Molecular Biology and Pathology of Human Elastin. Biochem Soc Trans. 19, 824-829.

  2. Li, D. Y., Brooke, B., Davis, E. C., Mecham, R. P., Sorensen, L. K., Boak, B. B., Eichwald, E., and Keating, M. T. (1998) Elastin is an Essential Determinant of Arterial Morphogenesis. Nature. 393, 276-280.

  3. Wendel, D. P., Taylor, D. G., Albertine, K. H., Keating, M. T., and Li, D. Y. (2000) Impaired Distal Airway Development in Mice Lacking Elastin. Am J Respir Cell Mol Biol. 23, 320-326.

  4. Rosenbloom, J. (1987) Elastin: An Overview. Methods Enzymol. 144, 172-196.

  5. Szabo, Z., Crepeau, M. W., Mitchell, A. L., Stephan, M. J., Puntel, R. A., Yin Loke, K., Kirk, R. C., and Urban, Z. (2006) Aortic Aneurysmal Disease and Cutis Laxa Caused by Defects in the Elastin Gene. J Med Genet. 43, 255-258.

  6. Micale, L., Turturo, M. G., Fusco, C., Augello, B., Jurado, L. A., Izzi, C., Digilio, M. C., Milani, D., Lapi, E., Zelante, L., and Merla, G. (2010) Identification and Characterization of Seven Novel Mutations of Elastin Gene in a Cohort of Patients Affected by Supravalvular Aortic Stenosis. Eur J Hum Genet. 18, 317-323.

  7. Ewart, A. K., Jin, W., Atkinson, D., Morris, C. A., and Keating, M. T. (1994) Supravalvular Aortic Stenosis Associated with a Deletion Disrupting the Elastin Gene. J Clin Invest. 93, 1071-1077.

  8. Ewart, A. K., Morris, C. A., Atkinson, D., Jin, W., Sternes, K., Spallone, P., Stock, A. D., Leppert, M., and Keating, M. T. (1993) Hemizygosity at the Elastin Locus in a Developmental Disorder, Williams Syndrome. Nat Genet. 5, 11-16.