AMPD3

AMP deaminase 3 is an enzyme that in humans is encoded by the AMPD3 gene.[5][6]

AMPD3
Identifiers
AliasesAMPD3, adenosine monophosphate deaminase 3
External IDsOMIM: 102772 MGI: 1096344 HomoloGene: 408 GeneCards: AMPD3
Orthologs
SpeciesHumanMouse
Entrez

272

11717

Ensembl

ENSG00000133805

ENSMUSG00000005686

UniProt

Q01432

O08739

RefSeq (mRNA)

NM_001172431
NM_000480
NM_001025389
NM_001025390
NM_001172430

NM_001276301
NM_009667
NM_001372439
NM_001372441

RefSeq (protein)

NP_000471
NP_001020560
NP_001020561
NP_001165901
NP_001165902

NP_001263230
NP_033797
NP_001359368
NP_001359370

Location (UCSC)Chr 11: 10.31 – 10.51 MbChr 7: 110.37 – 110.41 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

This gene encodes a member of the AMP deaminase gene family. The encoded protein is a highly regulated enzyme that catalyzes the hydrolytic deamination of adenosine monophosphate to inosine monophosphate, a branch point in the adenylate catabolic pathway. This gene encodes the erythrocyte (E) isoforms, whereas other family members encode isoforms that predominate in muscle (M) and liver (L) cells. Mutations in this gene lead to the clinically asymptomatic, autosomal recessive condition erythrocyte AMP deaminase deficiency. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.[6]

Model organisms

Model organisms have been used in the study of AMPD3 function. A conditional knockout mouse line, called Ampd3tm2a(KOMP)Wtsi[12][13] 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.[14][15][16]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[10][17] Twenty eight tests were carried out on mutant mice and four significant abnormalities were observed.[10] Mutant animals had increased IgG1 levels, increased trabecular bone thickness, decreased B cell numbers / increased granulocyte number and unusual brain histopathology (the thickness of the stratum radiatum was reduced and the dorsal 3rd ventricle area was increased).[10]

A second mouse line, called Ampd3T689A, was generated by ENU mutagenesis.[18] This mouse carries a mutation which increases AMPD3 function. Mutant animals have severely reduced erythrocyte lifespan, cyclic erythropoiesis, splenomegaly, and resistance to infection with Plasmodium chabaudi.[18]

References

  1. GRCh38: Ensembl release 89: ENSG00000133805 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000005686 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Mahnke-Zizelman DK, Sabina RL (October 1992). "Cloning of human AMP deaminase isoform E cDNAs. Evidence for a third AMPD gene exhibiting alternatively spliced 5'-exons". The Journal of Biological Chemistry. 267 (29): 20866–77. doi:10.1016/S0021-9258(19)36768-7. PMID 1400401.
  6. "Entrez Gene: AMPD3 adenosine monophosphate deaminase (isoform E)".
  7. "Peripheral blood lymphocytes data for Ampd3". Wellcome Trust Sanger Institute.
  8. "Salmonella infection data for Ampd3". Wellcome Trust Sanger Institute.
  9. "Citrobacter infection data for Ampd3". Wellcome Trust Sanger Institute.
  10. 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. S2CID 85911512.
  11. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  12. "International Knockout Mouse Consortium".
  13. "Mouse Genome Informatics".
  14. 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 (June 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.
  15. Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. S2CID 39281705.
  16. Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  17. van der Weyden L, White JK, Adams DJ, Logan DW (June 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.
  18. Hortle E, Nijagal B, Bauer DC, Jensen LM, Ahn SB, Cockburn IA, Lampkin S, Tull D, McConville MJ, McMorran BJ, Foote SJ, Burgio G (September 2016). "Adenosine monophosphate deaminase 3 activation shortens erythrocyte half-life and provides malaria resistance in mice". Blood. 128 (9): 1290–301. doi:10.1182/blood-2015-09-666834. PMC 5009516. PMID 27465915.

Further reading

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