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  • Undergraduate Poster Abstracts
  • Physiology/Pathology

    THU-368 NEUROBIOLOGICAL BASIS OF MENOPAUSAL HOT FLASHES

    • Alejandra Cabrera ;
    • Ashley Krull ;
    • Sarah Larsen ;
    • Jarrad Scarlett ;
    • Donald Clifton ;
    • Robert Steiner ;

    THU-368

    NEUROBIOLOGICAL BASIS OF MENOPAUSAL HOT FLASHES

    Alejandra Cabrera, Ashley Krull, Sarah Larsen, Jarrad Scarlett, Donald Clifton, Robert Steiner.

    University of Washington, Seattle, WA.

    Hot flashes (HF) are acute vasomotor disturbances that cause facial flushing and sweating. They commonly occur in menopausal women as a result of a decreased production of estradiol from the aging ovary which triggers an acute malfunction in the brain’s control of body temperature. However, the molecular and cellular mechanisms that generate HF are poorly understood. Recent studies suggest that super-activation of KNDy neurons in the hypothalamus, which occurs in response to either reduced levels of estradiol or artificial stimulation, can disrupt thermoregulatory centers in the brain. To test this, we are developing an optogenetic animal model for HF aimed at understanding their physiological origins and enabling preclinical testing of potential therapeutics. We have created a transgenic mouse that has a light-sensitive membrane channel (channelrhodopsin-2) inserted into KNDy neurons that can be activated with a fiber optic probe inserted into the brain. Selective activation of KNDy neurons and the subsequent behavioral response of the animal along a thermal gradient allow us to explore the role of KNDy neurons in thermoregulation. We hypothesize that following activation of KNDy neurons, the thermoregulatory setpoint for excess heat perception will be lowered, so the animal will move to a cooler place along the gradient. Testing this hypothesis is our primary objective. We believe development of an animal model for hot flashes will aid our understanding of their neurobiological basis and foster development of better and safer therapeutic options for treatment.

    FRI-367 GLUCAGON-LIKE PEPTIDE-1 RECEPTOR ACTIVATION AND ANGIOTENSIN RECEPTOR BLOCKADE DECREASE NADPH OXIDASE-4 PROTEIN EXPRESSION AND URINARY ALBUMIN EXCRETION IN A MODEL OF METABOLIC SYNDROME

    • Benny Escobedo ;
    • Ruben Rodriguez ;
    • Andrew Lee ;
    • Meagan Moreno ;
    • Akira Nishiyama ;
    • Rudy Ortiz ;

    FRI-367

    GLUCAGON-LIKE PEPTIDE-1 RECEPTOR ACTIVATION AND ANGIOTENSIN RECEPTOR BLOCKADE DECREASE NADPH OXIDASE-4 PROTEIN EXPRESSION AND URINARY ALBUMIN EXCRETION IN A MODEL OF METABOLIC SYNDROME

    Benny Escobedo1, Ruben Rodriguez1, Andrew Lee1, Meagan Moreno1, Akira Nishiyama2, Rudy Ortiz1.

    1University of California, Merced, Merced, CA, 2Kagawa Medical University, Miki-cho, Kita-gun, Kagawa, JP.

    Diabetic nephropathy is associated with oxidative stress and increased urinary albumin excretion. Angiotensin receptor type 1 (AT1) blockade improves renal oxidative stress via downregulation of NOX 4 and improves overall kidney damage by reducing albumin excretion. Glucagon-like peptide-1 receptor (GLP-1r) activation decreases glomerular NOX 4 expression and albumin excretion in streptozotocin-induced diabetic rats. To test the hypothesis that the combination of AT1 blockade and GLP-1r activation decreases oxidative stress and subsequent kidney damage, we measured renal NOX 4 protein expression and albumin excretion in 5 rat groups: untreated lean LETO (n = 7), untreated obese OLETF (n = 9), OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan /kg/d; n = 9), OLETF + GLP-1 mimetic (Exe; 10 ug exenatide/kg/d; n = 7), and OLETF + ARB + exenatide (combo; n = 6). Renal NOX 4 protein expression increased in OLETF compared to LETO. ARB and Exe decreased it, and combo treatment decreased it further. Albumin excretion increased in OLETF compared to LETO. ARB and Exe decreased it, and combo treatment decreased it further. These data suggest that AT1 blockade and GLP-1r activation ameliorate oxidative stress, highlighting the impact of the activation of these receptors in the pathogenesis of diabetes-associated renal impairments.

    FRI-368 ESTROGEN INCREASES VOLUNTARY EXERCISE BY OVARIECTOMIZED RATS

    • Enith Espinosa Palmett ;
    • Kathleen Curtis ;

    FRI-368

    ESTROGEN INCREASES VOLUNTARY EXERCISE BY OVARIECTOMIZED RATS

    Enith Espinosa Palmett1, Kathleen Curtis2.

    1Rogers State University, Claremore, OK, 2Center for Health and Sciences, Oklahoma State University, Tulsa, OK.

    The benefits of exercise on physical and psychological health are well-known. Exercise can be influenced by different physiological factors, including body fluid status. Estrogen is known to affect body fluid balance as well as locomotor activity. However, little is known about the effects of estrogen on voluntary exercise, and even less about how interactions between estrogen and body fluid challenges affect voluntary exercise. Previous studies in the lab suggest that water deprivation influences forced running. Thus, we hypothesized that estrogen and a body sodium challenge interact to affect voluntary running. Sixteen female Sprague-Dawley rats were bilaterally ovariectomized and allowed to recover for a week. They were then administered estradiol benzoate (EB) or oil on 2 consecutive days, repeated at weekly intervals for 3 weeks. Four oil-treated rats and 4 EB-treated rats were housed in cages in which running wheels were attached and were allowed to run voluntarily; 4 oil-treated rats and 4 EB-treated rats remained sedentary throughout the study. During weeks 1 and 3, running distance was recorded while rats were maintained on a regular diet (baseline 1 and 2). During week 2, running distance was recorded while rats were maintained on a sodium deficient diet (NaD). EB treatment increased distance running compared to oil treatment. Effects of NaD were modest; however, increased exercise experience increased distance running, particularly in EB-treaded rats. These results suggest that body fluid challenges affect voluntary running, but estrogen has a larger impact, especially with increasing exercise experience.

    FRI-371 RESISTANCE OF ERUCA SATIVA TO THE BACTERIAL BLIGHT PSEUDOMONAS CANNIBINA PV. ALISALENSIS

    • Saurina Beach ;
    • Carolee Bull ;
    • Polly Goldman ;

    FRI-371

    RESISTANCE OF ERUCA SATIVA TO THE BACTERIAL BLIGHT PSEUDOMONAS CANNIBINA PV. ALISALENSIS

    Saurina Beach1, Carolee Bull2, Polly Goldman2.

    1California State University, Monterey Bay, Seaside, CA, 2Agricultural Research Service, U.S. Department of Agriculture, Salinas, CA.

    Bacterial blight of crucifers caused by Pseudomonas cannabina pv. alisalensis results in significant crop loss worldwide. Identification of a resistant germplasm of arugula (Eruca sativa) could contribute to an economically viable disease management strategy for organic and conventional arugula production. Disease resistance was evaluated for 237 germplasm lines from the National Plant Germplasm System and 13 commercial cultivars. In preliminary experiments, each line was replicated twice with 5 plants per replication. Susceptible commercial cultivars were used as positive controls, and the most resistant commercial cultivars were used as negative controls. Three-week-old plants were spray inoculated with Pseudomonas cannibina pv. alisalensis grown on KMB and suspended in phosphate buffer to a concentration of approximately 108 CFU/ml. Plants were incubated at 100% humidity for 48 h and then moved to a greenhouse bench. Beginning 1 week after inoculation, disease severity on the most diseased leaf of each plant was rated weekly for 3 weeks on a scale of 1 to 6. The area under the disease progress curve was calculated and used in analyses. Results indicated that some lines may be resistant. Lines identified as resistant will now be compared to controls in experiments with more replication in order to determine if identified resistance is statistically and agronomically significant.

    THU-367 ANGIOTENSIN RECEPTOR BLOCKADE IMPROVES NON-ESTERIFIED FREE FATTY ACID AND TRIGLYCERIDE ACCUMULATION IN A RAT MODEL OF DIET-INDUCED OBESITY

    • Amy Hang ;
    • Andrew Lee ;
    • Akira Nishiyama ;
    • Rudy Ortiz1 ;

    THU-367

    ANGIOTENSIN RECEPTOR BLOCKADE IMPROVES NON-ESTERIFIED FREE FATTY ACID AND TRIGLYCERIDE ACCUMULATION IN A RAT MODEL OF DIET-INDUCED OBESITY

    Amy Hang1, Andrew Lee1, Akira Nishiyama2, Rudy Ortiz11.

    1University of California, Merced, Merced, CA, 2Kagawa Medical University, Miki-cho, Kita-gun, Kagawa, JP.

    Consumption of a high fat diet (HFD) overburdens the liver’s storage of fatty acids, contributing to non-esterified free fatty acid (NEFA) and triglyceride (TG) accumulation, leading to the development of hepatic steatosis and metabolic syndrome (MetS). Treatment with angiotensin receptor blocker (ARB) was previously shown to decrease hepatic lipid content, possibly improving hepatic steatosis. However, the impact that ARB treatment has on fatty acid storage and the development of hepatic steatosis in a rat model of MetS fed a HFD are unknown. To test the hypothesis that ARB decreases hepatic fatty acid storage in a rat model of MetS fed a HFD, the following groups were studied: Long-Evans Tokushima Otsuka (LETO, control) normal diet (ND), Otsuka Long-Evans Tokushima Fatty (OLETF ND), OLETF HFD (62% fat in food), OLETF ARB (10 mg olmesartan/kg/day), and OLETF HFD + ARB. HFD treatment increased body mass (14%) and liver mass (9%) relative to OLETF. HFD + ARB treatment decreased body mass (48%), liver mass (9%), plasma NEFA (17%), plasma TG (41%), and hepatic TG (44%) compared to HFD. These results demonstrate that ARB decreases hepatic TG accumulation in rats fed a HFD but was unable to completely restore them to control levels, suggesting that other obesity-associated factors are contributing to the impairment.

    THU-371 THE ROLE OF ANKRD2 IN INSULIN SENSITIVITY

    • Nhu Y Doan ;
    • Angelina Hernandez-Carretero ;
    • Olivia Osborn ;
    • Natalie Weber ;

    THU-371

    THE ROLE OF ANKRD2 IN INSULIN SENSITIVITY

    Nhu Y Doan, Angelina Hernandez-Carretero, Olivia Osborn, Natalie Weber.

    University of California, San Diego, La Jolla, CA.

    Insulin resistance is a characteristic feature of type-2 diabetes and plays a major role in the pathogenesis of the disease. Insulin resistance is defined as a reduced response of target tissues such as the skeletal muscle, liver, and adipocytes, to insulin. Skeletal muscle is the major site of glucose uptake in the postprandial state in humans. In this study we used RNA-seq to discover gene expression changes in mouse muscle in obesity and diabetes using lean, low fat (LF) fed mice and obese/diabetic, high fat (HF) diet fed mice. We found that expression of ankyrin repeat domain protein 2 (Ankrd2) was reduced in muscle from HF mice compared with LF diet fed mice. We hypothesized that Ankrd2 contributes to insulin sensitivity in the muscle and that reduction of Ankrd2 may impair insulin-stimulated glucose uptake. We used siRNA-mediated knockdown of Ankrd2 in rat L6 myotube cells and performed glucose uptake assays. Preliminary results show that approximately 75% knockdown of Ankrd2 expression impairs insulin-stimulated glucose uptake by 1.5-fold. This study will determine whether Ankrd2 is a useful therapeutic target to enhance the insulin sensitivity of obese and diabetic individuals.

    THU-370 ETB RECEPTORS PROMOTE NATRIURESIS IN RESPONSE TO AN ACUTE SALT LOAD IN MICE

    • Marcos Lucero ;
    • David Pollock ;
    • Joshua Speed ;

    THU-370

    ETB RECEPTORS PROMOTE NATRIURESIS IN RESPONSE TO AN ACUTE SALT LOAD IN MICE

    Marcos Lucero1, David Pollock2, Joshua Speed2.

    1University of California, Merced, Merced, CA, 2The University of Alabama at Birmingham, Birmingham, AL.

    Loss of renal endothelin B receptor (ETB) function results in salt-sensitive hypertension, and genetic mutation of the ETB receptor impairs the ability to excrete an acute salt load in rats. In order to probe the mechanisms, we designed experiments to develop a mouse model to determine whether loss of ETB function impairs the ability to excrete an acute salt load. Mice were treated with vehicle or the ETB antagonist, A-192621: 15 mg/kg given 3X at 24, 12, and 1 hour before starting an acute salt load. At the onset of their inactive period (lights on) mice were given 65 mg of NaCl in 300 µL of H2O by oral gavage, and urine was collected hourly for 8 hours. After gavage, mice treated with vehicle (H2O) had a significant increase in Na+ excretion compared to mice given ETB antagonist at 2 h (7.5 ± 1.2 vs. 0.03 ± 0.03 mg/2 h, respectively) and 4 h (8.9 ± 2.0 vs. 0.2 ± 0.1 mg/2 h, respectively, n = 4) post gavage. Interestingly, blockade of ETB receptors delayed the natriuretic response to an NaCl load, with the peak response of 9.3 ± 1.4 mg/2h occurring during hour 6. The peak response occurred at 2.5 ± 0.3 h in untreated mice vs. 5.0 ± 0.3 h in mice given the ETB antagonist. These data indicate that loss of ETB function in mice impairs the ability to excrete an acute salt load and provides evidence that genetically engineered mice may be an ideal model to probe the mechanisms by which ETB receptors maintain proper salt and H2O homeostasis.

    FRI-370 ROLE OF VASCULAR ENDOTHELIAL ENDOTHELIN-1 ON RENAL DAMAGE WITH HIGH SALT DIETS: ASSESSING SEX DIFFERENCES

    • Iris Montes ;
    • Carmen De Miguel ;
    • Jennifer Pollock ;

    FRI-370

    ROLE OF VASCULAR ENDOTHELIAL ENDOTHELIN-1 ON RENAL DAMAGE WITH HIGH SALT DIETS: ASSESSING SEX DIFFERENCES

    Iris Montes1, Carmen De Miguel, Jennifer Pollock.

    1University of California Merced, Merced, CA, 2The University of Alabama at Birmingham, Birmingham, AL.

    Dietary sodium intake is one of the main culprits in hypertension and kidney disease. Its effects are more prevalent in men than in pre-menopausal women of the same age. To assess sex differences in the role vasoactive peptide endothelin-1 (ET-1) has in the development of hypertension and kidney damage, vascular endothelial cell ET-1 knockout (VEET KO) mice of both sexes (12 weeks old; n = 5 - 7/group) were placed on high salt diets (4% NaCl) for 3 weeks. We hypothesized that the lack of ET-1 in the vasculature decreases the development of renal damage and this effect would be more prevalent in males.Water consumption, urine excretion, and urinary markers of renal damage were assessed at the end of the high salt period. Water consumption was uniform in both genotypes and sexes; however, urine production in male and female VEET KO mice was significantly reduced compared to Flox controls (Flox vs. VEET KO; Males: 2.6 ± 0.5 vs. 1.2 ± 0.4 ml/day; Females 3.0 ± 0.2 vs. 1.4 ± 0.2 ml/day; p < 0.05). KIM-1 excretion, a marker of proximal tubule damage, was significantly decreased in female VEET KO mice, compared to female Flox controls (6426.1 ± 1432.6 pg/day vs. 2539.0 ± 796.4 pg/day; p < 0.05), while there was no significant difference in both male genotypes. Results suggest that vascular endothelial ET-1 plays a larger role in the development of high salt-induced renal damage in males than in females.

    THU-369 THE POTENTIAL ROLE OF HOST ENGULFMENT PATHWAY IN ENTERIC INFECTION

    • Katherine Suarez ;
    • Rama Pranadinata ;
    • Amber Ablack ;
    • Lindsay Butcher ;
    • Sheila Crowe ;
    • Peter Ernst ;
    • Soumita Das ;

    THU-369

    THE POTENTIAL ROLE OF HOST ENGULFMENT PATHWAY IN ENTERIC INFECTION

    Katherine Suarez, Rama Pranadinata, Amber Ablack, Lindsay Butcher, Sheila Crowe, Peter Ernst, Soumita Das.

    University of California, San Diego, La Jolla, CA.

    The human gut maintains immunological homeostasis that distinguishes nonpathogenic and pathogenic enteric bacteria. While host cells recognize lipopolysaccharides on both pathogenic and nonpathogenic Gram-negative bacteria, the inflammatory response is induced primarily by pathogenic bacteria. We found that the engulfment and cell motility protein 1 (ELMO1) distinguishes pathogenic Salmonella and nonpathogenic E. coli, possibly through interactions with Salmonella effector protein SifA, a molecule that maintains the integrity of Salmonella-containing vesicles (SCV) and bacterial survival. Understanding how SifA interacts with host cells and contributes to disease pathogenesis can lead to new therapies for enteric bacteria. We developed a host model using enteroids from wild-type (WT) and ELMO1 knockout (KO) mice intestines that could be a bridge between cell lines and animal models. Enteroids were screened for ELMO1 expression and internalization of Salmonella. Internalization of Salmonella was tested by infecting WT and ELMO1 KO enteroids with Salmonella enetrica serovar typhimurium. Bacterial internalization was determined by plating assay to quantify the live bacteria present. Results showed a 5-fold decrease in internalization in enteroids isolated from ELMO1 KO mice compared to those from WT mice. The ELMO1 and SifA interaction was studied using full length, N- or C- terminal ELMO1 by immunopulldown assay and the result showed the interaction of SifA with the C- terminal of ELMO1. These results show that enteroids are a viable host model, and has helped clarify the location of SifA-ELMO1 binding for future research.

    FRI-366 BIOREACTIVITY AND CYTOTOXICITY OF COMMUNITY-ASSOCIATED METHICILLIN-RESISTANT (MRSA) METABOLITES

    • Maria Vides ;
    • Julieta Aguilar ;
    • Michael Dores ;

    FRI-366

    BIOREACTIVITY AND CYTOTOXICITY OF COMMUNITY-ASSOCIATED METHICILLIN-RESISTANT (MRSA) METABOLITES

    Maria Vides1, Julieta Aguilar2, Michael Dores2.

    1Pomona College, Claremont, CA, 2University of California, San Diego, La Jolla, CA.

    In recent years, methicillin-resistant Staphylococcus aureus (MRSA) has become a major challenge to public health, affecting 80,000 individuals each year and causing 11,000 deaths in the U.S. alone. Two main strains of MRSA have been identified, hospital-associated methicillin resistant S. aureus (HA-MRSA) and community-associated MRSA (CA-MRSA). Currently, the virulence of CA-MRSA is poorly understood. Using a peptidomics approach, 6 bioactive peptides were identified in CA-MRSA that are absent in HA-MRSA. These peptides robustly stimulate primary immune cells and cause lysis of blood cells. Since CA-MRSA typically cause skin and soft tissue infection, this study will test the effects of the 6 peptides on immune cells and skin cells. Preliminary results show that these peptides cause cell death. Further studies will identify the process of cell death by mass spectrometry and microscopy. This project will provide a new understanding of how CA-MRSA peptides damage mammalian tissues, and will lead to the development of new pharmacological avenues of intervention for the treatment of MRSA infections.

    FRI-369 PROTEIN EXPRESSION OF CD36 INCREASES AFTER INFUSION OF THYROID-STIMULATING HORMONE DURING PROLONGED-FASTING IN NORTHERN ELEPHANT SEAL PUPS

    • Lillian Horin ;
    • Bridget Martinez ;
    • Daniel E. Crocker ;
    • Rudy Ortiz ;

    FRI-369

    PROTEIN EXPRESSION OF CD36 INCREASES AFTER INFUSION OF THYROID-STIMULATING HORMONE DURING PROLONGED-FASTING IN NORTHERN ELEPHANT SEAL PUPS

    Lillian Horin1, Bridget Martinez2, Daniel E. Crocker3, Rudy Ortiz2.

    1Pitzer College, Los Angeles, CA, 2University of California, Merced, Merced, CA, 3Sonoma State University, Rohnert Park, CA.

    During a 2- to 3-month prolonged fast, northern elephant seals (NES) (Mirounga angustirostris) rely predominantly on non-esterified fatty acid (NEFA) oxidation to meet their energetic demands. Furthermore, NES experience an upregulation of cellular thyroid hormone (TH)-mediated components with fasting duration, an atypical response for food-deprived mammals. The functional relevance of the maintenance of TH-mediated signaling during prolonged food deprivation is unknown. To assess the association between TH and lipid metabolism in NES, we measured plasma NEFA concentrations and relative expression of CD36, an integral membrane protein that facilitates entry of long-chain fatty acids into the cell to begin β-oxidation, in response to thyrotropin (TSH) in early- (n = 4) and late- (n = 4) fasted pups. We hypothesized that the protein expression of CD36 increases with a TSH-induced increase in TH, an increase which will be more rapid and pronounced during the late fast. Late-fasted pups experienced a 60% ± 28.5 increase in the expression of CD36 after 60 min, a 2-fold increase compared to that of the early-fasted pups. Meanwhile, plasma NEFAs in the late-fasted seals increased by 48% ± 11 after 30 min, and decreased after 60 min. Furthermore, CD36 expression in late-fasted seals remained elevated, and plasma NEFA decreased to baseline levels. This suggests that prolonged fasting in NES pups increases sensitivity to TSH, and that THs contribute to the regulation of lipid metabolism via CD36 in northern elephant seal pups. A greater understanding of the contributions of THs to lipid metabolism may provide enhanced insight on TH-based therapies for metabolic disorders.

    THU-366 EVALUATING THE LINK BETWEEN PHYSIOLOGY AND MELANIN-BASED COLOR DIVERSITY IN AMNIOTES

    • Jessica Valdes ;
    • Chad Eliason ;
    • Julia Clarke ;

    THU-366

    EVALUATING THE LINK BETWEEN PHYSIOLOGY AND MELANIN-BASED COLOR DIVERSITY IN AMNIOTES

    Jessica Valdes, Chad Eliason, Julia Clarke.

    The University of Texas at Austin, Austin, TX.

    Colors in animals serve different functions such as protection from predators and mate attraction. The most common mechanism of coloration in reptiles, mammals, and birds is melanin-based coloration. Melanin pigment is contained in organelles known as melanosomes that tend to be larger and present in greater amounts in darker-colored vertebrates compared to lighter vertebrates. Melanin pigmentation in mice is altered by mutations in different genes, one of which, Gpnmb, affects the development of irides in mice. Osteoactivin (OA) in rats has been identified as identical to Gpnmb in mice and is known to play a role in other aspects of physiology, specifically bone growth. OA/Gpnmb has been identified as an ortholog to a key pigment gene, PMEL, that has been shown to affect melanosome shape. However, a correlation between changes in the melanin-based color system and the changes in Gpnmb known to affect bone growth has not been discovered. In order to determine if there is a relationship between these 2 aspects, we investigated whether melanosome shape was affected by changes in Gpnmb expression. We measured the aspect ratios of melanosomes in mouse hairs from 3 strains (wildtype, Gpnmb knockup, and Gpnmb knockout) and compared averages in male and female mice using a 2-sample t-test. Our results, for the first time, suggest a sex-related difference in melanosome shape caused by the knockout of Gpnmb in mice. When Gpnmb is up regulated, a sex-specific difference is not seen, however, melanosomes do become larger and rounder in both sexes.

    FRI-372 OVEREXPRESSION OF SARCOSPAN TO AMELIORATE PATHOLOGY ASSOCIATED WITH DYSTROPHIC CARDIOMYOPATHY

    • Abel Ferrel ;
    • Michelle Parvatiyar ;
    • Rachelle Crosbie-Watson ;

    FRI-372

    OVEREXPRESSION OF SARCOSPAN TO AMELIORATE PATHOLOGY ASSOCIATED WITH DYSTROPHIC CARDIOMYOPATHY

    Abel Ferrel, Michelle Parvatiyar, Rachelle Crosbie-Watson.

    University of California, Los Angeles, Los Angeles, CA.

    Progressive muscle wasting as seen in Duchenne muscular dystrophy (DMD) is the most commonly inherited disease in children, ultimately leading to respiratory and cardiac failure. Pathology originates from the lack of a dystrophin protein at the sarcolemma of muscle fibers. Dystrophin is part of a protein complex known as the dystrophin-glycoprotein complex (DGC), which links the extracellular matrix to the actin-cytoskeleton maintaining membrane stability and protecting against contraction-induced injury. Sarcospan (SSPN), a transmembrane component of the DGC, continues to reveal its potential as a therapeutic agent due to its stabilizing influence on the sarcolemma. Skeletal muscle studies on SSPN overexpressing mdx mouse lines (SSPN-TG:mdx) show recruitment of the utrophin-glycoprotein complex (UGC), a DGC-homologous complex. The UGC is normally located at the neuromuscular junction of striated muscle, but in SSPN-TG:mdx it displays extra-synaptic localization. In SSPN-TG:mdx hearts, levels of UGC proteins are anticipated to increase, thereby improving cardiomyocyte sarcolemmal stability relative to mdx controls. Histological methods, including hematoxylin and eosin, Mason’s trichome, and oil red staining will be performed to assess fibrosis and fat deposition, associated with DMD disease. Immunohistochemistry will be used to visually assess protein localization and relative abundance. Along with a decrease in contraction-induced damage, we anticipate that cardiac stress markers will be reduced when measured by qRT-PCR. The proposed studies are expected to further elucidate the role SSPN plays in stabilizing the sarcolemma of SSPN-TG:mdx hearts and inform the development of SSPN-based therapeutic strategies.