Reader TTS

ABSTRACT The eosinophil-associated ribonucleases (Ears) are rapidly evolving proteins found in multigene clusters that are unique to each rodent species. Of the 15 independent genes in the

_Mus musculus_ cluster, only mEars 1 and 2 are expressed at significant levels at homeostasis. Here we characterize the expression of mEar 6 in the liver and spleen in mice in response to

infection with the helminthic parasite, _Schistosoma mansoni_. Interestingly, expression of mEar 6 is not directly related to the elevated levels of serum IL-5 or tissue eosinophilia

characteristic of this disease, as no mEar 6 transcripts were detected in the liver or the spleen from uninfected IL-5-transgenic mice. The coding sequence of mEar 6 has diverged under

positive selection pressure (_K_a/_K_s>1.0) and has a unique unpaired cysteine near the carboxy-terminus of the protein. The high catalytic efficiency of recombinant mEar 6

(_k_cat/_K_m=0.9 × 106/M/s) is similar to that of the cluster's closest human ortholog, eosinophil-derived neurotoxin (EDN/RNase 2). In summary, we have identified mEar 6 as one of only

two RNase A superfamily ribonucleases known to be expressed specifically in response to pathophysiologic stress _in vivo_. Access through your institution Buy or subscribe This is a preview

of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 6 digital issues and online access to articles $119.00

per year only $19.83 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated

during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS NEUTROPHIL

METALLOPROTEINASE DRIVEN SPLEEN DAMAGE HAMPERS INFECTION CONTROL OF TRYPANOSOMIASIS Article Open access 05 September 2023 SPATIAL ADAPTATION OF EOSINOPHILS AND THEIR EMERGING ROLES IN

HOMEOSTASIS, INFECTION AND DISEASE Article 09 July 2024 GENOME-WIDE CRISPR SCREENING IDENTIFIES LRP1 AS AN ENTRY FACTOR FOR SFTSV Article Open access 29 April 2025 REFERENCES * Lander ES,

Linton LM, Birren B et al. Initial sequencing and analysis of the human genome. _Nature_ 2001; 409: 860–921. Article  CAS  Google Scholar  * Riordan J, D'Alessio G . _Ribonucleases:

Structures and Functions_. Academic Press: San Diego, 1997. Google Scholar  * Beintema JJ, Kleineidam RG . The ribonuclease A superfamily: general discussion. _Cell Mol Life Sci_ 1998; 54:

825–832. Article  CAS  Google Scholar  * Beintema JJ, Schuller C, Irie M, Carsana A . Molecular evolution of the ribonuclease superfamily. _Prog Biophys Mol Biol_ 1988; 51: 165–192. Article

  CAS  Google Scholar  * Rosenberg HF . The eosinophil ribonucleases. _Cell Mol Life Sci_ 1998; 54: 795–803. Article  CAS  Google Scholar  * Rosenberg HF, Dyer KD, Tiffany HL, Gonzalez M .

Rapid evolution of a unique family of primate ribonuclease genes. _Nat Genet_ 1995; 10: 219–223. Article  CAS  Google Scholar  * Zhang J, Rosenberg HF, Nei M . Positive Darwinian selection

after gene duplication in primate ribonuclease genes. _Proc Natl Acad Sci USA_ 1998; 95: 3708–3713. Article  CAS  Google Scholar  * Zhang J, Dyer KD, Rosenberg HF . Evolution of the rodent

eosinophil-associated RNase gene family by rapid gene sorting and positive selection. _Proc Natl Acad Sci USA_ 2000; 97: 4701–4706. Article  CAS  Google Scholar  * Larson KA, Olson EV,

Madden BJ et al. Two highly homologous ribonuclease genes expressed in mouse eosinophils identify a larger subgroup of the mammalian ribonuclease superfamily. _Proc Natl Acad Sci USA_ 1996;

93: 12370–12375. Article  CAS  Google Scholar  * Singhania NA, Dyer KD, Zhang J et al. Rapid evolution of the ribonuclease A superfamily: adaptive expansion of independent gene clusters in

rats and mice. _J Mol Evol_ 1999; 49: 721–728. Article  CAS  Google Scholar  * Cormier SA, Yuan S, Crosby JR et al. TH2-mediated pulmonary inflammation leads to the differential expression

of ribonuclease genes by alveolar macrophages. _Am J Respir Cell Mol Biol_ 2002; 27: 678–687. Article  CAS  Google Scholar  * Cormier SA, Larson KA, Yuan S et al. Mouse eosinophil-associated

ribonucleases: a unique subfamily expressed during hematopoiesis. _Mamm Genome_ 2001; 12: 352–361. Article  CAS  Google Scholar  * Nittoh T, Hirakata M, Mue S, Ohuchi K . Identification of

cDNA encoding rat eosinophil cationic protein/eosinophil-associated ribonuclease. _Biochim Biophys Acta_ 1997; 1351: 42–46. Article  CAS  Google Scholar  * McDevitt AL, Deming MS, Rosenberg

HF, Dyer KD . Gene structure and enzymatic activity of mouse eosinophil-associated ribonuclease 2. _Gene_ 2001; 267: 23–30. Article  CAS  Google Scholar  * Moreau JM, Dyer KD, Bonville CA et

al. Diminished expression of an antiviral ribonuclease in response to pneumovirus infection _in vivo_. _Antiviral Res_ 2003; 59: 181–191. Article  CAS  Google Scholar  * Yang D, Rosenberg

HF, Chen Q et al. Eosinophil-derived neurotoxin (EDN), an antimicrobial protein with chemotactic activities for dendritic cells. _Blood_ 2003; 102: 3396–3403. Article  CAS  Google Scholar  *

Sabin EA, Kopf MA, Pearce EJ . _Schistosoma mansoni_ egg-induced early IL-4 production is dependent upon IL-5 and eosinophils. _J Exp Med_ 1996; 184: 1871–1878. Article  CAS  Google Scholar

  * Dent LA, Strath M, Mellor AL, Sanderson CJ . Eosinophilia in transgenic mice expressing interleukin 5. _J Exp Med_ 1990; 172: 1425–1431. Article  CAS  Google Scholar  * Tominaga A,

Takaki S, Koyama N et al. Transgenic mice expressing a B cell growth and differentiation factor gene (interleukin 5) develop eosinophilia and autoantibody production. _J Exp Med_ 1991; 173:

429–437. Article  CAS  Google Scholar  * Rosenberg HF, Domachowske JB . Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens. _J Leukoc

Biol_ 2001; 70: 691–698. CAS  PubMed  Google Scholar  * Zhang J, Zhang YP, Rosenberg HF . Adaptive evolution of a duplicated pancreatic ribonuclease gene in a leaf-eating monkey. _Nat Genet_

2002; 30: 411–415. Article  CAS  Google Scholar  * Hoffmann KF, McCarty TC, Segal DH et al. Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal

type 1 and type 2 cytokine-mediated inflammatory reactions. _FASEB J_ 2001; 15: 2545–2547. Article  CAS  Google Scholar  * Rosenberg HF, Domachowske JB . Eosinophil-derived neurotoxin.

_Methods Enzymol_ 2001; 341: 273–286. Article  CAS  Google Scholar  * Bystrom J, Wynn TA, Domachowske JB, Rosenberg HF . Gene microarray analysis reveals interleukin-5-dependent

transcriptional targets in mouse bone marrow. _Blood_ 2004; 103: 868–877. Article  Google Scholar  Download references ACKNOWLEDGEMENTS We are deeply indebted to Dr James Lee and Dr Nancy

Lee, Mayo Scottsdale, for their generous gift of polyclonal anti-mEars antiserum and to Dr Klaus Matthaei, Australian National University, Canberra, Australia, for his gift of RNA samples

from IL-5 transgenic mice. We are also grateful to the staff of the NIAID 14BS Animal Facility for the care of the mice used in these studies. This work was partly supported by a JSPS

Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH (2004–2006). AUTHOR INFORMATION Author notes * T Nitto: JSPS Research Fellow in Biomedical and Behavioral

Research at NIH. AUTHORS AND AFFILIATIONS * Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA T Nitto, 

K D Dyer, R A Mejia, J Byström & H F Rosenberg * Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

T A Wynn Authors * T Nitto View author publications You can also search for this author inPubMed Google Scholar * K D Dyer View author publications You can also search for this author

inPubMed Google Scholar * R A Mejia View author publications You can also search for this author inPubMed Google Scholar * J Byström View author publications You can also search for this

author inPubMed Google Scholar * T A Wynn View author publications You can also search for this author inPubMed Google Scholar * H F Rosenberg View author publications You can also search

for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to T Nitto. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nitto, T., Dyer,

K., Mejia, R. _et al._ Characterization of the divergent eosinophil ribonuclease, mEar 6, and its expression in response to _Schistosoma mansoni_ infection _in vivo_. _Genes Immun_ 5,

668–674 (2004). https://doi.org/10.1038/sj.gene.6364143 Download citation * Received: 19 July 2004 * Revised: 13 September 2004 * Accepted: 13 September 2004 * Published: 04 November 2004 *

Issue Date: 01 December 2004 * DOI: https://doi.org/10.1038/sj.gene.6364143 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link

Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * _Schistosoma mansoni_ *

ribonuclease * eosinophils * interleukin-5