Request for Information (RFI): The Use and Maintenance of Antibody Allotype-defined Rabbits for Biomedical Research

Notice Number: NOT-AI-08-035

Key Dates
Release Date:  March 7, 2008
Response Date: April 7, 2008

Issued by
National Institute of Allergy and Infectious Diseases (NIAID), (http://www.niaid.nih.gov)

Description

The NIAID is actively seeking input from the scientific community to assess (1) scientific interest in maintaining certain unique rabbit strains for research purposes, and (2) interest from research or commercial groups in serving as a central facility to continue the breeding and distribution of these strains.

A unique pedigreed rabbit colony was developed and supported for many years at the NIAID, and a relational database containing more than 45 years of breeding records and other information about the animals in the colony was developed and maintained continuously to date. This rabbit colony will be discontinued unless alternative methods are identified to maintain the resource. At a minimum, 60-90 rabbits must be maintained and routinely bred to continue the three specific allotype lines described below, and at the same time prevent inbreeding at other genetic loci. Thus, appropriate veterinary and animal husbandry expertise is needed, as well as genetic typing capability and experience with animal tracking, shipping, and distribution. Basic housing and veterinary care currently require approximately $200,000 per year.

These rabbits have been uniquely valuable for studies on the genetics of the immune system, the regulation of B cell development and differentiation, antibody repertoire development, mucosal immunology, HIV-1 and other infectious diseases, and antibody-mediated autoimmune diseases. They are defined for immunoglobulin allotypes, which are allelic variants of antibody heavy and light chains. Three valuable strains are included in the colony and are designated as b9/b9, ali/ali, and the parental wild type 2R1/2R1. The b9/b9 rabbits were shown to be optimal for production of chimeric rabbit:human monoclonal antibodies with high affinities and specificity for antigen. The mutant ali/ali animals have a deletion in a key variable region gene in the immunoglobulin heavy chain locus that is present in the related wild type 2R1/2R1. These animals may differ in susceptibility to infectious disease because the mutant ali/ali has abnormally delayed development of humoral immunity; B lymphocyte development is delayed and depends heavily on gene conversion. These rabbits also provide a rich source of activation-induced deaminase enzyme and are a potential source for cofactor discovery.

Clearly, rabbits are useful models in a wide variety of additional research areas including cardiovascular, ocular, and neurological diseases. Therefore, antibody allotype markers, or the specific properties of these particular rabbit strains, may be advantageous for study in these areas as well. Furthermore, rabbit genomic information is now available: the rabbit genome has been sequenced at light 2X coverage, the trace archive of the whole genome shotgun sequence is available, and deep sequencing is underway at the Broad Institute. These advances may lead to increased utilization of rabbits in future research. Further information and journal references can be found at http://www3.niaid.nih.gov/research/resources/ri/news/0110rabbit.htm and http://www.ncbi.nlm.nih.gov/projects/genome/guide/rabbit/.

Information Requested

This RFI invites the scientific community to respond to one or more of the questions listed below. Responses are encouraged from investigators or science administrators at academic, government, and commercial institutions, as well as non-profit research agencies.

  1. Would your future research and development plans benefit from the availability of these rabbits? Provide a brief description of your R&D plans and how these rabbits would assist in achieving your research aims. Would additional information about these rabbits help you determine their future usefulness?
  2. Are you interested in supporting a colony of these rabbits, to continue their breeding and distribution to other investigators? Would it be feasible for you to do so? Under what circumstances would you be able to provide this service?
  3. Do your current research and development activities depend on continued availability of these allotype-defined rabbits? Provide a brief description of your R&D activities and how these rabbits assist in achieving your research aims. If the rabbits become unavailable, what modifications would you make to sustain your research program? What obstacles or barriers would you anticipate in completing your studies?

This RFI is for information and planning purposes only and should not be construed as a solicitation or as an obligation on the part of the Government. The Government does not intend to award any funds on the basis of responses to this RFI nor otherwise pay for the preparation of any information submitted or for the Government’s use of such information. Acknowledgement of receipt of responses will not be made, nor will respondents be notified of the Government’s evaluation of the information received. Responses will be held in a confidential manner. Any proprietary information submitted should be so marked.

Responses

Responses must be submitted by the date listed above. Responses are limited to 10 pages maximum length, and should be marked wit this RFI identifier: RFI-AI-08-034. Please send all responses by e-mail to hquill@niaid.nih.gov.

Inquiries

Administrative inquiries regarding this Notice may be directed to:

Helen Quill, Ph.D.
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
National Institutes of Health
6610 Rockledge Drive, Room 3013
Bethesda, MD 20892-6601 (use 20817 for express mail)
301-496-7551 Phone
301-480-2381 Fax
hquill@niaid.nih.gov

Scientific inquiries regarding this rabbit resource may be directed to:

Rose Mage, Ph.D.
Laboratory of Immunology
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Bethesda, MD 20892-1892
301-496-6113 Phone
301-496-0222 Fax
rmage@niaid.nih.gov


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