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The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. Differential impact on pulmonary and immunologic abnormalities.

Publication ,  Journal Article
Blackburn, MR; Aldrich, M; Volmer, JB; Chen, W; Zhong, H; Kelly, S; Hershfield, MS; Datta, SK; Kellems, RE
Published in: J Biol Chem
October 13, 2000

Adenosine deaminase (ADA) deficiency results in a combined immunodeficiency brought about by the immunotoxic properties of elevated ADA substrates. Additional non-lymphoid abnormalities are associated with ADA deficiency, however, little is known about how these relate to the metabolic consequences of ADA deficiency. ADA-deficient mice develop a combined immunodeficiency as well as severe pulmonary insufficiency. ADA enzyme therapy was used to examine the relative impact of ADA substrate elevations on these phenotypes. A "low-dose" enzyme therapy protocol prevented the pulmonary phenotype seen in ADA-deficient mice, but did little to improve their immune status. This treatment protocol reduced metabolic disturbances in the circulation and lung, but not in the thymus and spleen. A "high-dose" enzyme therapy protocol resulted in decreased metabolic disturbances in the thymus and spleen and was associated with improvement in immune status. These findings suggest that the pulmonary and immune phenotypes are separable and are related to the severity of metabolic disturbances in these tissues. This model will be useful in examining the efficacy of ADA enzyme therapy and studying the mechanisms underlying the immunodeficiency and pulmonary phenotypes associated with ADA deficiency.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 13, 2000

Volume

275

Issue

41

Start / End Page

32114 / 32121

Location

United States

Related Subject Headings

  • Thymus Gland
  • Spleen
  • Severe Combined Immunodeficiency
  • S-Adenosylhomocysteine
  • Phenotype
  • Mice, Transgenic
  • Mice
  • Lymphopenia
  • Lymphocytes
  • Lymphocyte Count
 

Citation

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Blackburn, M. R., Aldrich, M., Volmer, J. B., Chen, W., Zhong, H., Kelly, S., … Kellems, R. E. (2000). The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. Differential impact on pulmonary and immunologic abnormalities. J Biol Chem, 275(41), 32114–32121. https://doi.org/10.1074/jbc.M005153200
Blackburn, M. R., M. Aldrich, J. B. Volmer, W. Chen, H. Zhong, S. Kelly, M. S. Hershfield, S. K. Datta, and R. E. Kellems. “The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. Differential impact on pulmonary and immunologic abnormalities.J Biol Chem 275, no. 41 (October 13, 2000): 32114–21. https://doi.org/10.1074/jbc.M005153200.
Blackburn, M. R., et al. “The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. Differential impact on pulmonary and immunologic abnormalities.J Biol Chem, vol. 275, no. 41, Oct. 2000, pp. 32114–21. Pubmed, doi:10.1074/jbc.M005153200.
Blackburn MR, Aldrich M, Volmer JB, Chen W, Zhong H, Kelly S, Hershfield MS, Datta SK, Kellems RE. The use of enzyme therapy to regulate the metabolic and phenotypic consequences of adenosine deaminase deficiency in mice. Differential impact on pulmonary and immunologic abnormalities. J Biol Chem. 2000 Oct 13;275(41):32114–32121.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

October 13, 2000

Volume

275

Issue

41

Start / End Page

32114 / 32121

Location

United States

Related Subject Headings

  • Thymus Gland
  • Spleen
  • Severe Combined Immunodeficiency
  • S-Adenosylhomocysteine
  • Phenotype
  • Mice, Transgenic
  • Mice
  • Lymphopenia
  • Lymphocytes
  • Lymphocyte Count