A5089077432- Biochemical Analysis and Sensing Techniques
- melanin and skin pigmentation
- Epigenetics and DNA Methylation
- Regulation of Appetite and Obesity
- Animal Genetics and Reproduction
- Congenital heart defects research
- Genetics and Neurodevelopmental Disorders
- Amino Acid Enzymes and Metabolism
- Cellular transport and secretion
- Neurological diseases and metabolism
- Mitochondrial Function and Pathology
- Neurobiology and Insect Physiology Research
- Alzheimer's disease research and treatments
- Hedgehog Signaling Pathway Studies
- Prion Diseases and Protein Misfolding
- Hepatitis Viruses Studies and Epidemiology
- Infant Nutrition and Health
- Clinical Nutrition and Gastroenterology
- CRISPR and Genetic Engineering
- Renal and related cancers
- Genetic Mapping and Diversity in Plants and Animals
- Hepatitis B Virus Studies
- Metabolism and Genetic Disorders
- Olfactory and Sensory Function Studies
- Kruppel-like factors research
McLaughlin Research Institute
2014-2025
Touro College
2025
Cedars-Sinai Smidt Heart Institute
2024
Cedars-Sinai Medical Center
2024
Cornell University
2002-2013
Great Falls Clinic
2013
New York State College of Veterinary Medicine
2009-2013
Pediatrics and Genetics
1997-2002
Stanford University
1997-2002
Howard Hughes Medical Institute
1997-2002
mahoganoid is a mouse coat-color mutation whose pigmentary phenotype and genetic interactions resemble those of Attractin (Atrn). Atrn mutations also cause spongiform neurodegeneration. Here, we show that null for causes similar age-dependent neuropathology includes many features prion diseases but without accumulation protease-resistant protein. The gene mutated in encodes RING-containing protein with E3 ubiquitin ligase activity vitro. Similarities phenotype, expression, suggest genes are...
Twenty-one families were selected from the published reports in which propositus had triad of juvenile diabetes mellitus, insipidus, and optic atrophy. The data consistent with hypothesis an autosomal gene which, homozygote, causes mellitus one or more atrophy, nerve deafness. Heterozygotes appear to have increased probability developing mellitus.
The mouse mutations mahogany (mg) and mahoganoid (md) are negative modifiers of the Agouti coat color gene, which encodes a paracrine signaling molecule that induces swithc in melanin synthesis from eumelanin to pheomelanin. Animals mutant for md or mg synthesize very little no pheomelanin depending on gene background. protein is normally expressed skin acts as an antagonist melanocyte receptor alpha-MSH (Mc1r); however, ectopic expression causes obesity, possibly by antagonizing...
The solute carrier family 1 member 4 (SLC1A4) gene encodes a neutral amino acid transporter, also referred to as alanine-serine-cysteine transporter 1, ASCT1, that helps maintain balance in the brain and periphery. In brain, SLC1A4 plays important roles transporting levo(L) dopa(D) isomers of serine. L-serine is required for many cellular processes, including protein sphingolipid synthesis, while D-serine co-agonist normal neurotransmission through N-methyl-D-aspartate receptors. Through its...
Myelinating Schwann cells are particularly susceptible to defects in endosomal trafficking. TSG101 is a component of the trafficking machinery that mediates sorting ubiquitinated receptors into multivesicular bodies. We previously demonstrated deleting Tsg101 from mouse oligodendrocytes central nervous system causes rapid onset de/dys-myelination and vacuolation white matter, suggesting an important role for TSG101-dependent myelination. Here, we show also required normal myelination...
E3 ubiquitin ligases play a crucial role in modulating receptor stability and signaling at the cell surface, yet mechanisms governing their substrate specificity remain incompletely understood. Mahogunin Ring Finger 1 (MGRN1) is membrane-tethered ligase that fine-tunes sensitivity by targeting surface receptors for ubiquitination degradation. Unlike cytosolic ligases, E3s require transmembrane adapters to selectively recognize regulate receptors, few such have been studied detail. While...
FOXG1 syndrome is a severe neurodevelopmental disorder characterized by microcephaly, profound intellectual disability with communication deficits including lack of speech, impaired social interaction, increased anxiety, hyperkinetic/dyskinetic movements, seizures and abnormal sleep patterns. Mutations in single allele the gene cause disease, likely due to loss-of-function. However, current therapies do not target this root have little modest therapeutic benefit on only small subset...
Forward genetic screens with ENU (N-ethyl-N-nitrosourea) mutagenesis can facilitate gene discovery, but mutation identification is often difficult. We present the first study in which an ENU-induced was identified by massively parallel DNA sequencing. This causes heterotaxy and complex congenital heart defects mapped to a 2.2-Mb interval on mouse chromosome 7. Massively sequencing of entire 2 single-base substitutions, one intergenic region second causing replacement highly conserved...
Attractin, initially identified as a soluble human plasma protein with dipeptidyl peptidase IV activity that is expressed and released by activated T lymphocytes, also has been the product of murine mahogany gene connections to control pigmentation energy metabolism. The product, however, transmembrane protein, raising possibility membrane attractin in addition secreted form. genomic structure reveals arises from transcription 25 sequential exons on chromosome 20p13, where 3′ terminal exon...
Mutations that affect the balance between synthesis of eumelanin and pheomelanin provide a powerful set tools with which to understand general aspects cell signaling. Previous work from our laboratory has demonstrated is triggered by ability Agouti protein inhibit signaling through Melanocortin 1 receptor (Mc1r). In bioassay based on Xenopus Mc1r, two effects, competitive inhibition occupancy α‐MSH down‐regulation signaling, are mediated separately domains in amino‐ carboxy‐terminal regions...
Abstract Mutations of the mouse Attractin (Atrn; formerly mahogany) gene were originally recognized because they suppress Agouti pigment type switching. More recently, effects independent have been recognized: mice homozygous for Atrnmg-3J allele are resistant to diet-induced obesity and also develop abnormal myelination vacuolation in central nervous system. To better understand pathophysiology relationship these pleiotropic effects, we further characterized molecular abnormalities...
Abstract Mahogunin Ring Finger 1 ( Mgrn1 ) encodes a RING‐containing protein with ubiquitin ligase activity that has been implicated in pigment‐type switching. In addition to having dark fur, mice lacking MGRN1 develop adult‐onset spongy degeneration of the central nervous system and have reduced embryonic viability. Observation complete situs inversus small proportion adult mutant suggested lethality resulted from congenital heart defects due defective establishment and/or maintenance...
To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis dogs.1,551 dogs. Procedures-Hip conformation was measured radiographically. The FBN2 sequenced from genomic DNA of 21 Labrador Retrievers Greyhounds, haplotype intron 30 90 additional 143 dogs 6 other breeds. Steady-state values mRNA control genes were joint tissues fourteen 8-month-old Retriever-Greyhound crossbreeds.The homozygous for 10-bp deletion had...
The metalloprotease-disintegrin family, or ADAM, proteins, are implicated in cell-cell interactions, cell fusion, and signaling, widely distributed among metazoan phyla. Orthologous relationships have been defined for a few ADAM proteins including ADAM10 (Kuzbanian), ADAM17 (TACE), but evolutionary not clear the majority of family members. Human ADAM33 refers to testis cDNA clone that does contain complete open reading frame, portions predicted protein similar Xenopus laevis ADAM13.In 48 kb...