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ITP Collaborative Interactions Program FAQs

Summary of program

The ITP's Collaborative Interactions Program (CIP) was established to facilitate research by multiple laboratories on drugs that may retard aspects of aging and increase healthy lifespan in mice. A listing of specific drugs tested in each ITP cohort is available.

Several kinds of mice and tissues can be provided to researchers working on problems related to drug actions on health, aging, and age-related disease. These include:

  • Fixed tissues from mice at the end of their lifespan, treated with drugs tested by ITP laboratories.
  • Fixed tissues taken from mice euthanized at 22 months of age, for selected treatment groups. At present these are limited to mice treated with rapamycin and NDGA. Tissues from acarbose-treated mice will become available by the end of 2016, with others added in the next several years.
  • Frozen tissues taken at 22 months of age from mice treated with drugs used in C2015 and later annual cohorts. Control tissues from untreated, age-matched mice, and from young untreated mice, can also be provided.
  • Live, untreated mice at a variety of ages from 2 - 24 months. These animals can be used to evaluate whether specific experimental endpoints show age-related changes in the reproducible, genetically heterogeneous mouse stock, UM-HET3, that is used by the ITP.
  • Live mice for mice treated with agents used in C2015 and later cohorts may also be available in limited numbers.

Individuals interested in use of these materials for collaborative research projects should prepare a proposal describing their plans, typically 2 - 5 pages, with information about the assay(s) to be performed and giving details as to tissues, quantity and form (e.g. frozen, fixed, live) of material needed for the work, and the numbers of animals of each control and treatment group needed. The note should be sent to Dr. Francesca Macchiarini. Since availability of tissues, and especially live mice, is limited, proposals that allow for sharing of materials among laboratories are particularly encouraged. Interested researchers are encouraged to contact Dr. Macchiarini, or one of the three site directors listed below, for discussions of research ideas during the development of their formal proposal.

David Harrison, The Jackson Laboratory

Richard A. Miller, University of Michigan

Randy Strong, University of Texas Health Science Center

Key methodological details useful for proposal design

The ITP uses genetically heterogeneous mice, bred from a cross between (BALB/cByJ x C57BL/6J)F1 hybrid mothers and (C3H/HeJ x DBA/2J)F1 hybrid fathers. Thus each mouse is genetically unique, and can be considered a full sib of each other mouse in the colony with respect to nuclear genome. The cross is readily reproducible using the following parents available from The Jackson Laboratory: Dams: CByB6F1/J, JAX #100009; Sires C3D2F1/J; JAX #100004.

Variability of phenotypes is expected to be similar to that seen in inbred mouse stocks. Coefficients of variance for age at death, and for body weight, for two examples, are well within the range of those seen for collections of inbred mice. Power calculations to estimate needed sample size can therefore safely be based, for most phenotypes, on data from inbred or F1 hybrid animals.

Mice are fed a standard chow diet, based on Purina 5LG6, with drug supplementation at doses listed on the ITP website.

Both male and female mice are available. Proposals should include studies of both male and female mice.

Mice in the ITP are housed at three test sites: TJL (the Jackson Laboratory), UM (University of Michigan), and UT (University of Texas Health Science Center at San Antonio). There is substantial variability among the three test sites. Female mice at each site have very similar lifespans, but control male mice at UM typically live 10% - 15% longer than males at TJL or UT, and both males and females at UM are typically lighter in weight than mice at the other test sites.

Median survival for female controls has ranged from 840 - 920 days over six consecutive annual cohorts, with no consistent site-to-site variation. Median survival for male controls at TJL and UT has ranged from 680 - 820 days in these six cohorts, and median survival for UM male controls has ranged from 790 - 930 days. Thus tissues from mice euthanized at 22 months (664 days) represents 75% of the median lifespan for females, approximately 89% of median for UT and TJL males, and approximately 77% of median for UM male controls.

Logistics

1: Fixed tissues at the end of lifespan. Mice at all three sites are combined in equal numbers for such studies. Mice that die spontaneously, or which are euthanized when severely ill, are fixed by making incisions in cranium, thorax, and abdomen, and submerging the specimen into fixative. Fixative-immersed specimens are kept at room temperature until needed for study. Variable post-mortem intervals, variable ages at death, and variation in the nature and severity of the terminal illness limits the usefulness of these specimens except for tissues (example: bone) that are stable to such fluctuations.

2. Fixed tissues taken from mice euthanized at 22 months. These materials are currently available for NDGA and rapamycin treated mice, and will be available for acarbose-treated mice by late 2016. Blocks of embedded tissues are available, from which sections can be cut for specific stains. The typical dissection protocol provides material from 22 tissues.

3. Frozen tissue archive. From C2015 onward, mice are being set aside for each tested drug to provide frozen tissues (and serum or plasma) from limited numbers of mice euthanized at age 22 months, along with tissues prepared in parallel from young and aged untreated animals. These tissues are held at all three sites for collaborations, which will typically involve a mixture of tissues from all three sites, and both sexes. There are also limited supplies of frozen tissues for some previous cohorts, including some treated with rapamycin, acarbose, or 17-a-estradiol.

4. Live untreated UM-HET3 mice can be provided, in limited numbers, from stocks set aside for this purpose at TJL and at UM. This resource is used in particular when a potential collaborator has an assay of interest but needs to assess whether the trait in question changes with age in UM-HET3 animals.

5. UM is maintaining a small colony of live mice treated with each of the drugs in C2015, C2016, and future years that could be used as the basis for collaborations. Arrangements could potentially be made for treatment of these mice at UM; for shipment of the mice to other institutions; or for travel of visiting investigators to UM for specific studies.

Expenses

In most cases, collaborating investigators will need to be able to pay for the costs of work done at their own institutions using ITP-derived materials. The ITP can send mice or tissue samples to collaborators without charge. Investigators who could not conduct their study without partial cost-sharing are invited to inquire about possibilities for partial subsidization of the work at their institution, which can be considered on a case-by-case basis.

Data sharing; publication policies

We would expect that all data produced by collaborators will be shared with the NIA's scientific coordinator and with the three site directors as in any other collaborative study. If the collaborative work produces results suitable for publication, including evidence of beneficial or harmful effects or no effects, we would expect that ITP researchers will help in data analysis and preparation of the resulting manuscript, with co-authorship arrangements when these are appropriate. We will not consider requests for collaboration which are intended to produce data that are to be kept confidential for proprietary use by commercial entities, since it is a major goal of the ITP that all ITP-supported results be made available for publication in peer-reviewed journals or other publicly accessible forms.