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CORE DESCRIPTIONS/FEES:
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Mouse Phenotyping CORE:
Core Description and Goals:
 The Mouse Phenotyping Core will provide expertise and equipment to provide the investigators associated with the DERC to more accurately phenotype their mice. Phenotypic characterization of mouse models of diabetes and its complications is important to link pathology and pathophysiologic mechanisms to human disease, to identify new mechanisms and new therapeutic targets, and to test novel treatments. Moreover, as a multitude of models can be created by transgenic and knockout techniques, there is increasing need for the ready availability of standardized diets, assays, protocols, and technology to easily and rapidly characterize the models. As increasing evidence links metabolic alterations to both the micro- and macrovascular complications of diabetes, it will be important to assess the metabolic, vascular dysfunction and target organ damage in the same models. This approach is key to investigations of diabetes, not only as a metabolic disease but importantly, as a vascular disease as well. The Mouse Phenotyping Core will not only link metabolic, cardiovascular and renal phenotyping, but will bring together and cross-fertilize expertise in these areas to ultimately prevent and treat diabetes and its vascular complications.
Core Services:
The staff of the Rodent Phenotyping core will provide consultation to the various research users in the design and interpretation of animal experiments. We will assist in the selection of appropriate animal models and techniques to demonstrate hypotheses. This will include the determination of the appropriate routes of administration for compounds and correct controls. For example, in the case of investigators who desire to produce various metabolic perturbations will provide dietary consultation. This could include the use of dietary components to produce diabetes or atherosclerosis.
We will provide training to the various investigators in the appropriate and correct administration of drugs or compounds required in their experiments. This would include but not be limited to gavage, timed pellets and osmotic minipump placement. We would provide training in the surgical techniques and the route of delivery most appropriate to their experiment. This could include catheter or cannula placement into a specific organ or vascular bed from an osmotic minipump.
Oral or interperitoneal glucose tolerance tests will be performed to determine the degree of diabetes present in the mice. The mice will be gavaged with a glucose solution 1 mg glucose/1 g of mouse body weight in the OGTT or injected IP in the case of the IPGTT. Blood samples will be collected prior to the administration of the glucose for time zero. The standard protocol will also collect blood at 15, 30, 60, 90 and 120 minutes post-glucose administration, but the time points for blood collection can be modified depending on the requirements of the user. Blood will be collected from the retro-orbital sinus in lightly anesthetized mice (isoflurane inhalant) using sterile heparinized, microcapillary tubes. The collected blood will be placed on ice immediately placed on ice. The plasma will be separated by centrifugation as quickly as possible and the samples frozen. The biochemistry core will determine plasma glucose and insulin levels.
Hyperinsulinemic, euglycemic clamps will be performed in order to determine the degree insulin resistance in the various experimental animals. This involves two separate procedures with a recovery period of 4-6 days between to allow healing and minimize stress. The first procedure involves the placement of a catheter into the right internal jugular vein of the mouse for infusion of insulin and glucose. The mice are anesthetized and the catheter placed with the other end of the catheter being burrowed under the skin and exteriorized in the scapular region. After the recovery period the mice are subjected to the clamp procedure after a fast of 6 hours. The mice are infused with insulin (18 mU/kg/min) begun with infusion of a 25% glucose solution also being infused until an euglycemic state of ~6 mM is reached. Blood samples will be will be collected at –40, -20, -10, 0,10, 20, 30, 40, 50, 60, 70, 80 and 90 minutes from the tail vein for determination of plasma glucose and insulin. The glucose infusion rate will be determined as a measure of insulin resistance. This procedure can be modified in consultation with the research users to include tracers, etc dependent on the needs of the experimental protocols.
This core will provide kidney function tests including 24 hour creatinine, serum creatinine and microalbuminuria. The core will provide metabolic cages for collection of urine and processing of the samples for this assays. We are a component of the Animal Models of Diabetic Complications Consortium (AMDCC) funded by the NIDDK/NHLBI and will be performing the kidney function assays in the standardized methods developed by that group. Other assays including tracer analyses, etc will be provided if the research users evidence sufficient interest.
Body composition will be performed post-mortem and will consist of extraction of the various components. The percentage of total body fat will be determined as described. Briefly, the animals will be sacrificed and the carcasses dried to remove all water. They will then be homogenized and the lipid extracted from an aliquot of the homogenate using a soxhlet apparatus. The lipid content of the homogenate will then be determined by gravimetric analysis.
Dexascan will be performed to determine both bone density and body fat percentage using the PIXImus mouse densitometer from GE medical systems. Lightly anesthetized mice will be placed on the platform and scanned using dual-energy x-ray absorptiometry. This scan takes 5 minutes to perform and the produced images are stored on computer media. Either summarized data or the images will be provided to the investigator as per their request.
Non-invasive blood pressures will be obtained from the mice using the BP-2000 Blood Pressure Analysis System from Visitech Systems, Inc (Apex, NC). The Visitech BP-2000 Blood Pressure Analysis System is the computerized, non-invasive tail-cuff system that has been shown to provide measurements equivalent to arterial catheter blood pressure measurements. The system allows for the simultaneous gathering of blood pressure measurements on up to four conscious mice maximizing efficiency. The system minimizes technician error, as the software will collect data in the same manner every time.
The system uses a photoelectric sensor to detect the pulse in the tail distal to a tail cuff. The detected pulse is displayed on the computer monitor and the cuff is inflated by the system. The mice are heated on a warm platform to increase blood flow to the tail improving the pulse detection, for better results. The computer monitors both the losses of pulse detection and tail cuff pressure and when the pulse decreases the systolic pressure for that station is saved. The mice will have ten systolic blood pressure measurements taken at every session and the mean of the measurements used.
Catheterized blood pressures: Mice will have sterile catheters (0.04 O.D. x 0.025 I.D., Micro-Renathane) filled with heparinized saline placed into the carotid and (50U/ml) tunneled subcutaneously to extrude at the back of the neck. Lines will be flushed with sterile saline and one day will be allowed for recovery from surgery. Following a one-hour adaptation period after connection to recording equipment, blood pressure will be recorded. This approach will provide awake, conscious blood pressure measurements.
Cardiac fibrosis quantification: Histology of the heart will be carried out in order to assess cardiac fibrosis in the ventricle. The animals will be killed with pentobarbital overdose and the heart is removed. The heart is weighed and coronal sections of the heart, taken at the equator of the ventricles, are immediately fixed with 10% formalin in PBS. Formalin fixed tissue is serially dehydrated, embedded in paraffin and 4:M thick cross sections are cut from both ventricles. The sections are stained with the collagen-specific stain, picrosirius red (Sirius Red F3BA in aqueous picric acid) and subjected to morphometric analysis for quantitation. This analysis is performed on an imaging system consisting of an Olympus microscope with a 4X objective and a video camera mounted on the eyepiece tube. The image is displayed on a high resolution monitor and digitized by a video frame grabber (PCVISION Plus, Imaging Technology) in an IBM compatible computer. A morphometric analysis program (OPTIMAS, Bioscan Inc.) is used to determine the area of fibrosis, which will be defined as area of picrosirius or trichrome stained fibers 20 images/section are scanned. Two investigators blinded to the treatment group will perform this work.
Echocardiography: An Apogee CX echocardiographic machine (ATL Interspec, Bothell, WA), is available in the Mouse Physiology Lab. This machine incorporates a wide bandwidth transducer with dynamically focused symmetrical annular array technology that can be shifted to carrier frequencies of 9.0, 7.5, or 5.0 MHz. Small needle ECG leads (Grass Instruments) are placed through the skin on the right and left upper extremities and the left leg and connected to the machine for ECG timing. Images are captured digitally on a standard IBM PC using an ATI 128 Wonder video capture card (ATI, Canada) and then analyzed using Sigmascan (SPSS Software) that is calibrated to the scale recorded on each echocardiographic exam.
Cardiac catheterization: To more carefully evaluate hemodynamic parameters and specifically evaluate diastolic properties of mice we will also perform cardiac catheterization. A 1.4 French micromanometer-tipped catheter (Millar Instruments) will be inserted into the right carotid and advanced until a left ventricular pressure tracing is visualized. Measurements are acquired with Hem Software (Notocord Systems, Croissy, France) and associated pressure and ECG amplifier system. Pressure and heart rate data are recorded after the injections. Parameters measured include heart rate, LV systolic pressure, LV end diastolic pressure, and arterial. pressure. LV dP/dt max, and LV dP/dtmin, as well as the time constant of isovolumic pressure decay (Tau), are calculated from the LV pressure tracing. Data is averaged over at least a 10 second period.
Pressure volume loops: To more rigorously examine cardiac function, pressure-volume loops will also be performed. Data obtained in this manner will detect complementary data to that obtained by standard invasive catheterization and echocardiography and may provide further evidence of subtle derangements of cardiovascular function. The left ventricle will be catheterized through an apical approach with a miniaturized impedance/micromanometer catheter (Millar Instruments). A limited lateral thoracotomy is then performed to expose the descending aorta. An ultrasound probe (Transonics Model#1RB) is then placed around the aorta. Then baseline parameters of pressure, impedance and aortic flow are acquired on the physiological acquisition system discussed above. Aortic flow is measured so that stroke volume can be determined from the beat-to-beat flow in the aorta and correlated with the non-calibrated conductance signal which is acquired simultaneously. In this manner, relative changes in ventricular volume can be determined.
En face atherosclerosis will be determined using the following method. Mice are sacrificed and perfused with 7.5% sucrose in 4% paraformaldehyde. Aortas were dissected out, split longitudinally, pinned flat in a dissection pan and stained with Sudan IV to detect lipids and determine lesion area. Images were captured using a Sony 3-CCD video camera and analyzed by a single technician who was blinded to the study using ImagePro image analysis software. Extent of atherosclerosis is expressed as the percentage of the total aortic surface area covered by lesions.
Aortic root atherosclerorotic lesion analysis will be performed in which the fixed heart sections beginning at the aortic valve are examined
Bone Marrow transplantation: Bone marrow cells are isolated by sterile dissection and flushing of the tibias and humeri. The cells are then washed several times and counted. The recipient mice are irradiated with a dose of 900 rads. The transplantation is achieved by tail vein injection of 2 million cells from the donors. The mice are then allowed to recover for 4 weeks prior to the introduction of diet or treatment.
Arterial injuries can be performed in both rats and mice by personnel associated with the Core. These include the balloon injury of carotids and aortae in rats and or wire injury of the carotids or femoral vessels in mice.
Collection, morphological and histological analyses of tissues can be done by the Core. The Core has personnel trained in the collection of tissues for light microscopy as well as electron microscopy. Morphological and histological analyses can be performed using stereomicroscopy, bright field microscopy, phase contrast microscopy and fluorescent microscopy. The Core has a Nikon 80i linked to the latest ImagePro software which includes the ability to tile images, producing merged high resolution images. Additionally, the Core can quantify the various cellular or histological components in the images.
Luminex multiplex analyses can be performed by the Core on plasma and cell culture media. The Luminex machine allows multiple ELISA reactions to be performed simultaneously on small samples of plasma or media. Assays that can be performed using this equipment also include forms of genetic analysis.
Fee Structure for Mouse Physiology Core
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Non-DERC Members |
DERC Members |
| Experimental Design Consultation |
N/A |
Free |
| Drug Delivery Training |
N/A |
Free |
| Glucose Tolerance Test |
$400/10 animals |
$300/10 animals |
| Euglycemic Clamp |
$200.00/animal |
$150/animal |
| Kidney Function Tests |
$75.00/animal |
$50/animal |
| Body Composition |
$600/10 animals |
$500/10 Animals |
| Dexascan |
$200/5 animals |
$150/5 animals |
| Computerized Tail Cuff Blood Pressure |
$20/animal |
$10/animal |
| Catheterized Blood Pressure |
$150/animal |
$130/animal |
| Quantification of Cardiac Fibrosis |
$400/animal |
$300/animal |
| Echocardigraphy |
$90/animal |
$75/animal |
| Cardiac Catheterization (Millar) |
$250/animal |
$200/animal |
| En face Atherosclerotic Quantification |
$80.00/animal |
$50/animal |
| Aortic Root Atherosclerotic Analysis |
$120/animal |
$80/animal |
| Bone Marrow Transplantation |
$250/animal |
$200/animal |
| Balloon Injury |
$150/animal |
$125/animal |
| Collection, Morphology and Histology |
N/A |
Variable |
| Assay Development (Novel) |
N/A |
Variable |
| Development and Dissemination of New Strains |
Shipping Dependent on particular assay |
Shipping Dependent on particular assay |
| Luminex Assays |
Shipping Dependent on particular assay |
Shipping Dependent on particular assay |
Core PI:
Willa A. Hsueh, M.D.
Alan R. Collins, Ph.D.
Core Contact:
Alan R. Collins, Ph.D.
Phone: 310-794-7555
FAX: 310-794-7654
e-mail: acollins@mednet.ucla.edu
- Transgenic and Knockout Mouse CORE:
Web Page: http://cancer.ucsd.edu/tgm/
Core Description and Goals:
It is clear that the progress of diabetes and endocrine research during the coming decade will depend upon the ability to utilize the mouse as an experimental model to investigate both basic and clinically relevant questions in diabetes and endocrine research. This core provides members of the DERC with the most advanced technologies for genetic modification of the mouse genome. Transgenic mice carrying new or novel genes are created by microinjection of DNA into the pronuclei of fertilized eggs and "Knock-out" or “Knock-in” mice lacking specific genes of interest or containing modified version of key genes are created by homologous recombination in embryonic stem cells followed by injection into blastocysts to create chimeric mice for breeding to homozygosity. Conditional expression and Cre/LoxP targeted knock-out strategies are provided. The high degree of conservation of most sequences in genomes of humans and mice makes the approach of using transgene and knock-out gene technology to create models of human diabetes and endocrine pathogenesis extremely attractive. This Core is an outstanding example of how extraordinarily specialized techniques, highly trained dedicated personnel, and expensive equipment can be accessed by researchers who could not reasonably expect to develop them on an individual basis. The availability of this Transgenic and Knock-out Mouse Core in coordination with the Mouse Phenotyping Core, the Transcriptional Genomics Core, and Biochemistry and Molecular Assay Core, will enable our members to conduct versatile, cutting-edge, reverse genetic research in the mouse with a battery of multidisciplinary state-of-the-art techniques.
The UCSD Transgenic Mouse and Embryonic Stem Cell Core Facility has been in operation since 1992. The key measures of success of a transgenic and knock-out mouse production facility, are the measures of quality and quantity of mice produced. In 2002, we performed 71 transgenic jobs. We achieved an average of 16.35% integration for approximately 5 positive found animals per job and almost a 100% success rate overall. We also have consistent success with large DNA molecules including the injection of BACs of greater than 100 kb.
Our ES cell electroporation to produce homologous recombination to produce either knock-in or knock-out animals has also been highly successful. In 2002, we performed 121 embryonic stem cell targeting jobs resulting in an average recombination efficiency of 2.32% for an average of 4.86 homologously recombined clones per job. For ES cell injection into blastocysts for the creation of chimeric mice, we have also been very successful. We performed 90 blast injection jobs with an average of 21.9 pups per job with an average of 5 highly chimeric animals resulting for each job. These chimeras range from 30% agouti up to 100%. Mice less than 30% chimeric are not counted as chimeras. We aim to deliver at least 5 highly chimeric animals per job and thus secure an eventual germ line transmission of the targeted gene.
Core Services:
Pronuclear Injection
A desired DNA construct is injected into the pronucleus of a 0.5 d.p.c. Embryo. Resulting pups are returned to the Client. The client will then analyze these by Southern blot to determine the presence of the given transgene.
Blastocyst Injection
Mouse Embryonic Stem cells that have undergone homologous recombination are injected into the blastocoel cavity of 3.5 d.p.c. blastocyst stage C57Bl6 Embryos. Injected blastocysts are implanted into pseudopregnant recipient females, and chimeric pups are born. Chimerics are returned to the Client. Those that transmit the 'knock-out' allele to germline produce agouti pups, which are analyzed for phenotype by the client.
Gene Targeting
A targeting vector containing a 'knock-out' or 'knock-in' gene of interest is electroporated into Mouse Embryonic Stem Cells (129 SvJ). The cells undergo drug selection, clones are picked and expanded in tissue culture, then returned to the Client for analysis. Homologous Recombinant clones are verified by the client using either PCR or Southern Blot analysis by the client.
Chromosome Count
Chromosome counting is done on targeted homologous recombinant ES cell clones prior to blastocyst injection for quality control.
Embryo Rederivation
Embryo Rederivation is used to create a pathogen free strain of mice from lines that arrive at the University from a non-approved vendor and mice contaminated with various pathogens (MHV, Pinworm, Parvovirus). Males arrive in the Rodent Isolation Unit (RIU), and wild-type females of the desired background strain are superovulated and mated to the males. Embryos are harvested in the RIU, washed and transferred into pathogen free, pseudopregnant recipient females, which are returned to the Client.
Ovary Transplants
Sexually mature females that are infertile or cannot carry a litter to term are ovariectomized. These ovaries are then transplanted into the wild-type ovariectomized females of a given background strain, and returned to the Client. Two weeks later, the recipients are mated by the client to produce transgenic pups of the original genotype.
Mouse Embryo Cryopreservation
Genetic banking through the use of mouse embryo cryopreservation is a practical means to store scientifically valuable mice. Mouse embryos stored in liquid nitrogen offer a safe way to preserve lines with potential future use but no current use and offer savings in facility space and the expense associated with keeping a breeding colony. Another advantage is that during the process of embryo collection, most pathogenic organisms are excluded as in other methods used to rederive lines of mice. Briefly, the procedure entails harvesting embryos from donor females at the 8-cell developmental stage that is optimal for cryopreservation by our method. A controlled-rate methanol bath freezer is used to gradually cool the embryos to -80°C, before plunging them into liquid nitrogen for storage. Quality control is assured by freezing and thawing a representative sample of wild-type frozen embryos along with each line frozen down. Frozen embryos should be retrieved by the investigator one week post-freezing for long-term storage in liquid nitrogen in the investigator's own lab.
2003 Core Prices
| |
DERC Member |
UCSD Other |
Non-UCSD* |
| Pronuclear Injection Hybrid Mouse Strain |
$2,619 |
$2,750 |
$3,905 |
| Pronuclear Injection Inbred Mouse Strain |
$3,143 |
$3,300 |
$4,686 |
| Blastocyst Injection |
$3,143 |
$3,300 |
$4,686 |
| ES-cell Gene Targeting (Knock-Out or Knock-In) |
$3,143 |
$3,300 |
$4,686 |
| ES-cell Gene Targeting (Cre-loxP) |
$5,238 |
$5,500 |
$7,810 |
| Chromosome Count |
$210 |
$220 |
$312 |
| Embryo Rederivation |
$1,048 |
$1,100 |
$1,562 |
| Ovary Transplant |
$733 |
$770 |
$1,093 |
| Embryo Freezing |
$1,309 |
$1,375 |
$1,953 |
*Prices are subject to change without notice.
Core PI:
Pamela L. Mellon, Ph.D.
pmellon@ucsd.edu
(858) 534-1312
Core Contacts:
http://cancer.ucsd.edu/tgm/
Pronuclear Injection (Transgenic Mice), Embryo Rederivation Contact
Jun Zhao, Core Manager
juzhao@ucsd.edu
858-822-3270
Gene Targeting (Embryonic Stem Cells and Blastocyst Injection) Contact
Ella Kothari, Core Manager
ekothari@biomail.ucsd.edu
858-534-3178
Embryo Cryopreservation (Embryo Freezing) Contact
Heather Oakley
hoakley@ucsd.edu
858-822-2108
- Transcriptional Genomics CORE:
BIOGEM
(BioMedical Genomics Microarray Facility)
Core Description and Goals:
 A major goal in efforts to understand the mechanisms by which signal transduction pathways regulate programs of gene expression is to identify their direct target genes in response to regulatory signals
The BIOGEM CORE Facility provides services to advance such efforts; conventional microarray analysis and early in 2004 promoter microarray analysis. Conventional microarray analysis will utilize glass slides spotted with PCR products corresponding to specific genes, allowing large-scale assessment of relative levels of gene expression. These arrays are intended to complement the use of commercially available microarrays (e.g., Amersham CodeLink microarrays). For example, microarrays containing a few hundred to a few thousand cDNA targets of particular interest can be printed at relatively low cost, allowing multiple experimental conditions to be examined that would be prohibitively expensive using commercially available arrays.
Core Services:
Custom Array production:
One of the major functions of the BIOGEM CORE Facility is to "print" cDNA microarrays from various clone and primer sets onto glass slides. BIOGEM offers assistance to investigators wishing to develop custom arrays targeted to a particular developmental stage, a specific cellular process or an organism with minimal genome sequence determined. The expertise available in BIOGEM allows researchers with minimal related experience to take full advantage of the microarray CORE services. As an example, BIOGEM prints a custom microarray of approximately 1000 cDNAs corresponding to genes of interest in metabolism, atherosclerosis and inflammation. Similar custom arrays could be fabricated for other sets of genes of interest, or for other species (e.g., human and rat).
Processing of Commercial Array Slides e.g. Amersham CodeLink™ Bioarrays:
The CodeLink™ system is a complete bioarray solution for high-performance gene expression profiling. CodeLink is an integrated platform that includes catalog and custom gene expression bioarrays, target preparation and bioarray processing reagents, and image analysis and QA/QC software.
The CodeLink™ system is particularly useful when carrying out experiments with very small amounts of RNA. Starting with small quantities total RNA is beneficial for several reasons. First, it results in decreased time, labor and costs associated with not having to purify poly(A)+RNA. Second, many samples (biopsy, for example) do not contain sufficient amounts of total RNA to enable purification of poly(A)+RNA. Such samples could only be processed if the small amount of present total RNA could be used. Third, the less the biological sample is manipulated, the lower the chance that artifacts due to RNA processing will be introduced. Finally, purification of poly(A)+RNA, typically performed on an oligo(dT) column, can bias the sample by enriching for polyadenylated transcripts.
In September 2002 BIOGEM became the official UCSD site for processing of CodeLink™ bioarrays. BIOGEM will provide target labeling, hybridizing and washing of CodeLink™ bioarrays in a service capacity. The investigator will provide RNA and BIOGEM will label the target, perform the hybridization and provide the user with raw and normalized microarray data.
Bioinformatics support.
BIOGEM has numerous public and commercial software tools available for data mining and is connected with numerous bioinformatics experts at UCSD who can provide additional advice.
Personnel training:
The CORE provides training for all DERC investigators engaged, or interested, in array-based research. This training includes assistance in designing and conducting array-based experiments, protocols for labeling fluorescent targets and hybridizing arrays.
Further array resources:
Further array resources are in development including fabricating promotor microarrays.
Recent progress in combining the use of chromatin immunoprecipitation (ChIP) assays with DNA microarrays has allowed genome-wide analysis of transcription factor localization to specific promoter sequences in living cells. BIOGEM is currently fabricating murine promoter microarrays to allow genome-wide location analysis of transcription factors such as nuclear hormone receptors and signal-dependent transcription factors. These arrays will be available in early 2004.
Core PI:
Dr. Chris Glass
Core Contact:
Dr. Gary Hardiman
University of California San Diego
2234 Bonner Hall
9500 Gilman Drive
La Jolla CA 92093-0349
Tel: 858-822-3792
Fax: 858-822-3021
email: ghardiman@ucsd.edu
www.biogem.ucsd.edu
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Human Genetics CORE:
Core Description and Goals:
 Recent successes in genetic mapping have demonstrated that the technological capability now exists to identify the genes responsible for complex disorders. To be successful in such endeavors, it is necessary to combine expertise in genetic epidemiology, clinical investigation, molecular genotyping, and mathematical genetic analysis. The goal of the Human Genetics Core is to offer such expertise to DERC investigators conducting studies into the genetics of diabetes, its complications and related endocrine disorders. In particular, the DERC offers an opportunity to facilitate research directed at identifying the genes responsible for Type 2 diabetes and insulin resistance related disorders including complications, by providing access to both the expertise and facilities necessary for such genetic research in human populations.
Core Services:
Assist DERC investigators with genetic study design
Establish and maintain EBV-transformed lymphoblastoid cell lines and generate nonviable cell pellets for DNA/RNA isolation
Development of a panel of anonymized lymphoblastoid cell lines from subjects well characterized for diabetes and/or insulin sensitivity which will be available to DERC investigators for such purposes as searching for mutations in specific candidate genes (This panel has not yet been developed but is anticipated to be available by summer, 2004)
Provide genotyping services including genome scans, microsatellite and SNP testing of candidate genes
Assist in the performance of a wide range of analytic techniques, including: segregation analysis, heritability estimation, population and family-based association, parametric and non-parametric linkage analysis, multi-point variance component linkage analysis, and linkage disequilibrium mapping
The Human Genetics Core will also provide training to DERC investigators and their staffs to enable them to perform many of these procedures themselves, with ongoing consultative support from Core staff.
Core PI’s:
Jerome I. Rotter, M.D.
Leslie J. Raffel, M.D.
Core Contact:
Cynthia Hernandez, R.N.
Genetics Study Coordinator
Division of Medical Genetics
Cedars-Sinai Medical Center
8700 Beverly Blvd. SSB378
Los Angeles, California 90048
Tel. (310) 423-1457
Fax (310) 423-0237
Cynthia.Hernandez@cshs.org
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