University of Pennsylvania / Johns Hopkins University School of Medicine Physiological Assessment Core

Center Institution(s)

University of Pennsylvania
Johns Hopkins University

Title of core facility or other resource

Physiological Assessment Core B
Scientific Research Resource Core

Contact person, email address, phone number

Elisabeth Barton, Ph.D.
Assistant Professor
Anatomy and Cell Biology
School of Dental Medicine
441 Levy Building, 240 S.40 th Street
University of Pennsylvania
erbarton@biochem.dental.upenn.edu
tel 215-573-0887/215-746-3096

Currently available or expected date of availability

Isolated muscle mechanical testing is now available for several muscles (EDL, soleus, diaphragm, masseter)

Whole animal testing (hindlimb suspension, free wheel running, treadmill running) is currently available on a limited basis

Muscle function on in situ preparations (e.g., tibialis anterior) is under development and is expected to be available within 6 months.

Requirements for use (by collaboration or fee-for-service, application required, etc.)

The first priority of Core B will be to perform the proposed experiments of this center grant's projects. However, it will also serve as a national resource and be available to members of the muscular dystrophy community for studies on a fee basis. Scheduling of internal or external projects will attempt to complete each data set within reasonable time windows, on a first come first serve basis. The amount of time needed for any given project can vary widely, as can the necessity for experiment design and data interpretation. Therefore, these issues will be addressed on a case-by-case basis. An advisory committee has been put in place to set priorities, especially in the event that demand on the core exceeds its capacity. Our current capacity can handle twice as much as is proposed in this MDCRC grant. If demand constantly exceeds our capacity, then additional personnel and equipment will be put in place.

Use of the core will be open to other investigators who need physiological assessment of their animals. This can be accomplished in one of two ways. For animals maintained at other institutions, animals to be tested will be shipped at the outside investigators' expense to the core for measurements within 72 hours of receipt. In some cases, this will require multiple shipments in order to follow animal housing guidelines of U. Penn. If longer housing is required, arrangements will need to be made for quarantine of these animals. Alternatively, we have started to maintain in-house colonies of mouse models for DMD, LGMD, and myotonic dystrophy, which can be used for outside investigators' studies. In this case, the per diem charges will become the responsibility of the outside investigator, as will the assurance of an approved animal protocol. While the protocol holder will be Dr. Barton, it will be the outside investigator's responsibility to write the protocol. For those outside the MDCRC, a charge of $50/hour will be assessed to cover the cost of technician time and supplies. For experiments involving housing of animals, animal housing charges will be borne by the outside user.

If requests for Core use from industry are received, charges will be negotiated on a case-by-case basis, where fees would not reflect the subsidies associated with NIH support.

While the Core will be available for all U.S. academic researchers, foreign investigators and industry will not automatically have access. Inquiries will be directed to the Advisory Committee and if the priority is high and the request can be accommodated without compromises MDCRC or U.S. academic research projects, cost recovery will be negotiated and one on a contractual basis.

Note that normal use of the Core will be on a fee basis and not on an authorship basis (although acknowledgment of the Core will be required in any resulting publications). Core use is meant to simply provide physiological measurements, with data and tissue returned to the Core user without interpretation. If more substantive experimental design, data interpretation, or guidance is needed, this can be discussed with the core director. If inexperience of an investigator requires a major experimental design effort on the part of either Dr. Barton or Dr. Sweeney, then a negotiated authorship on resulting publications may be appropriate and requested.

Brief description of services or resources (a paragraph or two)

The physiological assessment core will provide a wide range of methods to determine functional performance in dystrophic mouse models. The following table includes measurements available and muscles utilized for each measurement. Whole animal studies can be followed with in vitro measurements, as needed.

Measurement	Muscles studied	Parameters to be Assessed
In vitro mechanics
maximum tetanic force	EDL, Soleus, Diaphragm (strips)	force generating capacity
force-frequency profile	""	calcium handling shifts (fiber type)
eccentric contractions	""	susceptibility to contractile damage
In situ mechanics
maximum tetanic force	Tibialis Anterior	force generating capacity
force-frequency profile	""	calcium handling/fiber type profile
eccentric contractions	""	susceptibility to contractile damage
Whole animal manipulations
Hindlimb suspension	Soleus, Gastrocnemius, Plantaris	initiate disuse atrophy
Free-wheel running	whole animal	voluntary exercise
Weighted wheel running	whole animal; Plantaris, Soleus, TA	voluntary training
Downhill treadmill running	whole animal	contractile damage
Dye uptake studies
procion orange	in vitro mechanic muscls	sarcolemmal susceptibility to injury
Evan's blue dye	whole animal, target muscle groups	ongoing membrane damage
Blood CK levels	whole animal	ongoing membrane leakiness