Request for Information (RFI): Invitation to Comment on Effectiveness of an Earlier Request for Proposals (RFP) for A Repository of Mouse Models for Cytogenetic Disorders

Notice Number: NOT-HD-15-003

Key Dates
Release Date: March 12, 2015
Response Date: May 15, 2015

Related Announcements
None

Issued by
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Purpose

The Eunice Kennedy Shriver National Institute of Child Health and Human Development is interested in evaluating the results of the Request for Proposals (RFP) for “A Repository of Mouse Models for Cytogenetic Disorders” released in 2010. As part of this process, NICHD welcomes comments from the public concerning the ability of this repository to meet the needs of the research community, its accomplishments, and areas for improvement. NICHD welcomes suggestions concerning potential future research objectives that may be met by increasing the availability of specific rodent strains for cytogenetic disorders, particularly Down syndrome, to the research community.

Background

During the past 20 years, investigators have generated a number of murine models of human cytogenetic disorders, the most common of which is Down syndrome, which usually results from three copies of the entire human chromosome 21 (Trisomy 21) and occurs in ~1:691 live births each year. This contract to generate and distribute mouse models for cytogenetic disorders with special emphasis on mouse chromosome 16 (MMU16) began in the 1970s with the demonstration of genetic synteny between a segment of MMU16 and human chromosome 21 (HSA21). With the subsequent genetic dissection of both the mouse and human genomes, other genes present on HSA21 were localized to MMU17 and MMU10. Dr. Muriel Davisson of the Jackson Laboratory in Bar Harbor, ME, created partial trisomies for a number of syntenic chromosomal segments in the 1980s, under contract to NICHD. One of these trisomies, designated Ts65Dn, proved to include approximately 150 genes located in what is considered the “Down syndrome critical region” of HSA21, as well as a small number of genes located on MMU17 outside the HSA21 syntenic region. Subsequently, under a contract to NICHD, she produced and distributed these mice to investigators approved by NICHD.

Over the years, a number of murine models relevant to DS have been created. These include, but are not limited to Ts1Cje, Ts2Cje, Ts1Rhr, Ms1Rhr, and Tc1. Placing these strains and stocks in a central repository ensures their maintenance on appropriate genetic backgrounds and their timely distribution to the research community upon request and approval by NICHD. In 2010, the NICHD reissued the RFP “A Repository of Mouse Models of Cytogenetic Disorders” with a substantial increase in investment to ensure timely access to and increased availability of mouse models for cytogenetic disorders, particularly Ts65Dn, to the research community, and to ensure increased experimental efforts to modify the existing genetic backgrounds for the various strains to increase availability and ease of use by investigators. An RFI, NOT-HD-11-002 “Request for Information (RFI): Acquisition, Processing, Storage and Distribution of Human Brain and Other Tissues to Advance Understanding and Treatment of Down Syndrome” was released in 2011, and a substantial number of responses identified the need for increased availability of the mouse models to the research community as a priority issue. Subsequently, at a workshop “Advancing Treatment for Alzheimer Disease in Individuals with Down Syndrome” held in April, 2013, the Alzheimer disease and DS research and advocacy communities joined to advance the diagnosis and treatment of Alzheimer’s disease in individuals with Down syndrome. One weakness identified by the participants in this meeting was the limited availability of existing model systems (other than the Ts65Dn mouse) to the research community at large. Since that meeting, the partial duplication strains Dup(16)Yey, Dup(17)Yey, and Dup(10)Yey have become available. Each of these strains contains a duplication of one of the 3 mouse chromosome regions that are syntenic to HSA21, with Dup(16)Yey representing the largest number of murine genes syntenic to the human chromosome 21.

Information requested

The NICHD invites the research, advocacy, self-advocate, and family communities to comment on the following:

  • Ability of the Repository to meet the needs of the research community over the last five years
  • Specific needs for availability of existing mouse model for Down syndrome within the Repository
  • Additional rodent models that may be available in the research community but not a part of the existing Repository
  • Any activities that the Repository could undertake that might increase the utility or stability of existing mouse models for Down syndrome
  • Critical current needs for rodent models of Down syndrome that should be developed to advance research in Down syndrome research, including early developmental aspects of the condition as well as later-onset Alzheimer’s disease
  • Long-term needs of the research community for other models of Down syndrome or other cytogenetic disorders

The information obtained from the community will help inform NICHD in how best to update the Repository and ensure that the specific rodent models needed for the study of Down syndrome are available for the next five years.

How to Submit a Response

Responses will be accepted until May 15, 2015. All responses must be submitted via email to DSRDRFI@mail.nih.gov. Please include the notice number NOT-HD-15-003 in the subject line and include your complete contact information with your response. The submitted information will be reviewed by the NICHD and members of the Trans-NIH Down Syndrome Working Group. Submitted information will not be considered confidential.

Inquiries

Please direct all inquiries to:

Melissa A. Parisi, MD, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6880
Email: parisima@mail.nih.gov