SMARCAL1
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1 is a protein that in humans is encoded by the SMARCAL1 gene.[1][2][3]
Function
The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The SMARCAL1 protein convert RPA-bound, single stranded DNA into double-stranded DNA, an enzyme activity termed "annealing helicase".[4]
The encoded protein shows sequence similarity to the E. coli RNA polymerase-binding protein HepA. Mutations in this gene are a cause of Schimke immunoosseous dysplasia (SIOD), an autosomal recessive disorder with the diagnostic features of spondyloepiphyseal dysplasia, renal dysfunction, and T-cell immunodeficiency.[3]
Model organisms
| Characteristic | Phenotype |
|---|---|
| Homozygote viability | Normal |
| Homozygous Fertility | Normal |
| Body weight | Normal |
| Anxiety | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Hot plate | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Body temperature | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology | Normal |
| Peripheral blood lymphocytes | Normal |
| Heart weight | Normal |
| Brain histopathology | Abnormal |
| All tests and analysis from[5][6] |
Model organisms have been used in the study of SMARCAL1 function. A conditional knockout mouse line, called Smarcal1tm1a(EUCOMM)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty tests were carried out and one significant phenotype was observed: homozygous mutant mice had abnormal brain histopathology, including an enlarged hippocampus and a thickened hippocampus stratum oriens.[5]
References
- ↑ Muthuswami R, Truman PA, Mesner LD, Hockensmith JW (Mar 2000). "A eukaryotic SWI2/SNF2 domain, an exquisite detector of double-stranded to single-stranded DNA transition elements". The Journal of Biological Chemistry 275 (11): 7648–55. doi:10.1074/jbc.275.11.7648. PMID 10713074.
- ↑ Coleman MA, Eisen JA, Mohrenweiser HW (May 2000). "Cloning and characterization of HARP/SMARCAL1: a prokaryotic HepA-related SNF2 helicase protein from human and mouse". Genomics 65 (3): 274–82. doi:10.1006/geno.2000.6174. PMID 10857751.
- 1 2 "Entrez Gene: SMARCAL1 SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a-like 1".
- ↑ Yusufzai T, Kadonaga JT (Oct 2008). "HARP is an ATP-driven annealing helicase". Science 322 (5902): 748–50. doi:10.1126/science.1161233. PMC 2587503. PMID 18974355. Lay summary – ScienceDaily (2008-11-02).
- 1 2 3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
- ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ↑ "International Knockout Mouse Consortium".
- ↑ "Mouse Genome Informatics".
- ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Further reading
- Boerkoel CF, Takashima H, John J, Yan J, Stankiewicz P, Rosenbarker L, André JL, Bogdanovic R, Burguet A, Cockfield S, Cordeiro I, Fründ S, Illies F, Joseph M, Kaitila I, Lama G, Loirat C, McLeod DR, Milford DV, Petty EM, Rodrigo F, Saraiva JM, Schmidt B, Smith GC, Spranger J, Stein A, Thiele H, Tizard J, Weksberg R, Lupski JR, Stockton DW (Feb 2002). "Mutant chromatin remodeling protein SMARCAL1 causes Schimke immuno-osseous dysplasia". Nature Genetics 30 (2): 215–20. doi:10.1038/ng821. PMID 11799392.
- Lou S, Lamfers P, McGuire N, Boerkoel CF (Dec 2002). "Longevity in Schimke immuno-osseous dysplasia". Journal of Medical Genetics 39 (12): 922–5. doi:10.1136/jmg.39.12.922. PMC 1757210. PMID 12471207.
- Bökenkamp A, deJong M, van Wijk JA, Block D, van Hagen JM, Ludwig M (Dec 2005). "R561C missense mutation in the SMARCAL1 gene associated with mild Schimke immuno-osseous dysplasia". Pediatric Nephrology 20 (12): 1724–8. doi:10.1007/s00467-005-2047-x. PMID 16237566.
- Clewing JM, Antalfy BC, Lücke T, Najafian B, Marwedel KM, Hori A, Powel RM, Do AF, Najera L, SantaCruz K, Hicks MJ, Armstrong DL, Boerkoel CF (Feb 2007). "Schimke immuno-osseous dysplasia: a clinicopathological correlation". Journal of Medical Genetics 44 (2): 122–30. doi:10.1136/jmg.2006.044313. PMC 2598061. PMID 16840568.