Michael Grzybowski
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View article: Aberrant recursive splicing in a human disease locus
Aberrant recursive splicing in a human disease locus Open
Recursive splice sites are rare motifs postulated to facilitate splicing across massive introns and shape isoform diversity, especially for long, brain-expressed genes. The necessity of this unique mechanism remains unsubstantiated, as doe…
View article: Chromatin interaction maps of human arterioles reveal mechanisms for the genetic regulation of blood pressure
Chromatin interaction maps of human arterioles reveal mechanisms for the genetic regulation of blood pressure Open
Arterioles are small blood vessels located just upstream of capillaries in nearly all tissues. Despite the broad and essential role of arterioles in physiology and disease, current knowledge of the functional genomics of arterioles is larg…
View article: Physiological role and mechanisms of action for a long noncoding haplotype region
Physiological role and mechanisms of action for a long noncoding haplotype region Open
View article: A Mutation in the Transmembrane Domain of <i>Adenylate Cyclase 3</i> Impairs Enzymatic Function to Cause Sex‐Specific Depression‐ and Anxiety‐Like Behaviors and Food Seeking in a Rat Model
A Mutation in the Transmembrane Domain of <i>Adenylate Cyclase 3</i> Impairs Enzymatic Function to Cause Sex‐Specific Depression‐ and Anxiety‐Like Behaviors and Food Seeking in a Rat Model Open
We have previously demonstrated that a transmembrane domain mutation in Adenylate cyclase 3 ( Adcy3 ) causes increased adiposity and negative emotion‐like behaviors in a rat model. We set out to replicate and expand upon our previous study…
View article: A mutation in the transmembrane domain of <i>Adenylate cyclase 3</i> impairs enzymatic function to cause sex-specific depression- and anxiety-like behaviors and food seeking in a rat model
A mutation in the transmembrane domain of <i>Adenylate cyclase 3</i> impairs enzymatic function to cause sex-specific depression- and anxiety-like behaviors and food seeking in a rat model Open
We have previously demonstrated that a transmembrane domain mutation in Adenylate cyclase 3 ( Adcy3 ) causes increased adiposity and negative emotion-like behaviors in a rat model. We set out to replicate and expand upon our previous study…
View article: A single-cell map of hypertension
A single-cell map of hypertension Open
Hypertension is a leading risk factor for disease burden and death worldwide. Several organ systems are involved in the development of hypertension, which contributes to stroke, heart disease, and kidney disease. Despite the broad health r…
View article: Chromatin interaction maps of human arterioles reveal new mechanisms for the genetic regulation of blood pressure
Chromatin interaction maps of human arterioles reveal new mechanisms for the genetic regulation of blood pressure Open
Arterioles are small blood vessels located just upstream of capillaries in nearly all tissues. The constriction and dilation of arterioles regulate tissue perfusion and are primary determinants of systemic blood pressure (BP). Abnormalitie…
View article: Protein-coding mutation in<i>Adcy3</i>increases adiposity and alters emotional behaviors sex-dependently in rats
Protein-coding mutation in<i>Adcy3</i>increases adiposity and alters emotional behaviors sex-dependently in rats Open
1 Abstract Objective Adenylate cyclase 3 (Adcy3) has been linked to both obesity and major depressive disorder (MDD). Our lab identified a protein-coding variant in the 2 nd transmembrane (TM) helix of Adcy3 in rats, and similar obesity va…
View article: Physiological role and mechanisms of action for a long noncoding haplotype region
Physiological role and mechanisms of action for a long noncoding haplotype region Open
Most common sequence variants associated with human traits are in noncoding regions of the genome, form haplotypes with other noncoding variants, and exhibit small effect sizes in the general population. Determining the physiological roles…
View article: Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype
Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype Open
Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene. The Col7a1 gene codes for collagen type VII protein, a major component of anchoring fibrils. Mutations of the Col7a1 gene can caus…
View article: Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3
Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of Krtcap3 Open
We previously identified Keratinocyte-associated protein 3 , Krtcap3 , as a novel adiposity gene, but subsequently found that its impact on adiposity may depend on environmental stress. To more thoroughly understand the connection between …
View article: Changes in environmental stress over COVID-19 pandemic likely contributed to failure to replicate adiposity phenotype associated with <i>Krtcap3</i>
Changes in environmental stress over COVID-19 pandemic likely contributed to failure to replicate adiposity phenotype associated with <i>Krtcap3</i> Open
Obesity is linked to both genetics and environmental factors such as stress. Krtcap3 has previously been identified as a gene associated with adiposity, and our work here demonstrates that environmental stress may influence the role of Krt…
View article: Chronic Stress Increases Adiposity and Anxiety in Rats with Decreased Expression of<i>Krtcap3</i>
Chronic Stress Increases Adiposity and Anxiety in Rats with Decreased Expression of<i>Krtcap3</i> Open
We previously identified Keratinocyte-associated protein 3 , Krtcap3 , as a novel adiposity gene but subsequently found that its impact on adiposity may depend on environmental stress. To more thoroughly understand the connection between K…
View article: Changes in Environmental Stress over COVID-19 Pandemic Likely Contributed to Failure to Replicate Adiposity Phenotype Associated with<i>Krtcap3</i>
Changes in Environmental Stress over COVID-19 Pandemic Likely Contributed to Failure to Replicate Adiposity Phenotype Associated with<i>Krtcap3</i> Open
We previously identified Keratinocyte-associated protein 3, Krtcap3, as an obesity-related gene in female rats where a whole-body Krtcap3 knock-out (KO) led to increased adiposity compared to wild-type (WT) controls when fed a high-fat die…
View article: Genetic Disruption of System xc-Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat
Genetic Disruption of System xc-Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat Open
The importance of neuronal glutamate to synaptic transmission throughout the brain illustrates the immense therapeutic potential and safety risks of targeting this system. Astrocytes also release glutamate, the clinical relevance of which …
View article: <i>Sry</i>-modified laboratory rat lines to study sex-chromosome effects underlying sex differences in physiology and disease: Four Core Genotypes and more
<i>Sry</i>-modified laboratory rat lines to study sex-chromosome effects underlying sex differences in physiology and disease: Four Core Genotypes and more Open
Background Previous research on Four Core Genotypes and XY* mice has been instrumental in establishing important effects of sex-chromosome complement that cause sex differences in physiology and disease. We have generated rat models using …
View article: Genetic mapping of multiple metabolic traits identifies novel genes for adiposity, lipids and insulin secretory capacity in outbred rats
Genetic mapping of multiple metabolic traits identifies novel genes for adiposity, lipids and insulin secretory capacity in outbred rats Open
Despite the successes of human genome-wide association studies, the causal genes underlying most metabolic traits remain unclear. We used outbred heterogeneous stock (HS) rats, coupled with expression data and mediation analysis, to identi…
View article: Genetic Mapping of Multiple Traits Identifies Novel Genes for Adiposity, Lipids, and Insulin Secretory Capacity in Outbred Rats
Genetic Mapping of Multiple Traits Identifies Novel Genes for Adiposity, Lipids, and Insulin Secretory Capacity in Outbred Rats Open
Despite the successes of human genome-wide association studies, the causal genes underlying most metabolic traits remain unclear. We used outbred heterogeneous stock (HS) rats, coupled with expression data and mediation analysis, to identi…
View article: Genetic mapping of multiple metabolic traits identifies novel genes for adiposity, lipids and insulin secretory capacity in outbred rats
Genetic mapping of multiple metabolic traits identifies novel genes for adiposity, lipids and insulin secretory capacity in outbred rats Open
Despite the successes of human genome-wide association studies, the causal genes underlying most metabolic traits remain unclear. We used outbred heterogeneous stock (HS) rats, coupled with expression data and mediation analysis, to identi…
View article: Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females
Keratinocyte-associated protein 3 plays a role in body weight and adiposity with differential effects in males and females Open
Despite the obesity crisis in the United States, the underlying genetics are poorly understood. Our lab previously identified Keratinocyte-associated protein 3, Krtcap3, as a candidate gene for adiposity through a genome-wide association s…
View article: Genetic Disruption of System xc- Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat
Genetic Disruption of System xc- Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat Open
The impact of CNS disorders is exacerbated by the difficulty in developing safe, effective glutamatergic therapeutics. Synaptic glutamate transmission is vital for neural physiology throughout the brain, which contributes to the vast thera…
View article: <i>Btg2</i> mutation induces renal injury and impairs blood pressure control in female rats
<i>Btg2</i> mutation induces renal injury and impairs blood pressure control in female rats Open
Hypertension (HTN) is a complex disease influenced by heritable genetic elements and environmental interactions. Dietary salt is among the most influential modifiable factors contributing to increased blood pressure (BP). It is well establ…
View article: <i>Keratinocyte-Associated Protein 3</i> is a novel gene for adiposity with differential effects in males and females
<i>Keratinocyte-Associated Protein 3</i> is a novel gene for adiposity with differential effects in males and females Open
Objective Despite the obesity crisis in the United States, the underlying genetics are poorly understood. Our lab previously identified Keratinocyte-associated protein 3, Krtcap3, as a candidate gene for adiposity where increased expressio…
View article: UBASH3A deficiency accelerates type 1 diabetes development and enhances salivary gland inflammation in NOD mice
UBASH3A deficiency accelerates type 1 diabetes development and enhances salivary gland inflammation in NOD mice Open
View article: CRISPR-Mediated Single Nucleotide Polymorphism Modeling in Rats Reveals Insight Into Reduced Cardiovascular Risk Associated With Mediterranean <i>G6PD</i> Variant
CRISPR-Mediated Single Nucleotide Polymorphism Modeling in Rats Reveals Insight Into Reduced Cardiovascular Risk Associated With Mediterranean <i>G6PD</i> Variant Open
Epidemiological studies suggest that individuals in the Mediterranean region with a loss-of-function, nonsynonymous single nucleotide polymorphism (S188F), in glucose-6-phosphate dehydrogenase ( G6pd ) are less susceptible to vascular dise…
View article: Robust and replicable measurement for prepulse inhibition of the acoustic startle response
Robust and replicable measurement for prepulse inhibition of the acoustic startle response Open
Measuring animal behavior in the context of experimental manipulation is critical for modeling, and understanding neuropsychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral phenomenon studied exten…
View article: Robust and replicable measurement for prepulse inhibition of the acoustic startle response
Robust and replicable measurement for prepulse inhibition of the acoustic startle response Open
Measuring animal behavior in the context of experimental manipulation is critical for modeling and understanding neuro-psychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral paradigm used extensivel…
View article: Water quality and physical hydrogeology of the Amarapura township, Mandalay, Myanmar
Water quality and physical hydrogeology of the Amarapura township, Mandalay, Myanmar Open
Mandalay is a major city in central Myanmar with a high urban population and which lacks a central wastewater management system, a solid waste disposal process, and access to treated drinking water. The purpose of this study is to investig…
View article: A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease
A NOX4/TRPC6 Pathway in Podocyte Calcium Regulation and Renal Damage in Diabetic Kidney Disease Open
Background Loss of glomerular podocytes is an indicator of diabetic kidney disease (DKD). The damage to these cells has been attributed in part to elevated intrarenal oxidative stress. The primary source of the renal reactive oxygen specie…
View article: Phosphorylation of Cardiac Mitochondrial VDAC1 at S215 Facilitates Cell Death
Phosphorylation of Cardiac Mitochondrial VDAC1 at S215 Facilitates Cell Death Open