Our laboratory studies genetic disorders of human growth and reproduction, focusing on obesity and subtle chromosome abnormalities.
Our work addressing obesity involves understanding the function of SIM1, a hypothalamic transcription factor implicated in body weight regulation by a mutation in a girl with severe, early onset obesity. Sim1 mutant mice show a similar phenotype, with enhanced susceptibility to diet-induced obesity. These mice have defective hypothalamic melanocortin and oxytocin signaling. We are presently studying the molecular and neuroanatomic basis for this defect using mouse models.
We recently identified a microduplication affecting another hypothalamic transcription factor in a girl with severe, unexplained obesity. We plan to model this duplication in transgenic mice to determine if it causes her obesity.
Other studies in the lab involve characterizing a novel X chromosome microdeletion syndrome and cryptic chromosome abnormalities associated with birth defects (in collaboration with pediatric urologists, surgeons, and cardiologists). The lab also has an active collaboration with a pediatric endocrinologist to study cognitive deficits associated with sex chromosome abnormalities, including Turner syndrome (45,X) and Klinefelter syndrome (47,XXY).
RESEARCH INTERESTS
Obesity
Chromosome abnormalities
Copy number variation
RECENT PUBLICATIONS
Kublaoui BM, Holder JL Jr, Gemelli T, Zinn AR., "Sim1 haploinsufficiency impairs melanocortin-mediated anorexia and activation of paraventricular nucleus neurons." Mol Endocrinol, 20:2483-2492, Fall 2006
Kublaoui BM, Holder JL Jr, Tolson KP, Gemelli T, Zinn AR, "SIM1 overexpression partially rescues agouti yellow and diet-induced obesity by normalizing food intake." Endocrinology, 147:4542-4549, Fall 2006
Zinn AR, Roeltgen D, Stefanatos G, Ramos P, Elder F, Kushner H, Kowal K, Ross JL, "A Turner syndrome neurocognitive phenotype maps to Xp22.3." Behavioral Brain Functions, 3:24, Spring 2007
Jaeckle Santos LJ, Xing C, Barnes RB, Ades LC, Megarbane A, Vidal C, Xuereb A, Tarpey PS, Smith R, Khazab M, Shoubridge C, Partington M, Futreal A, Stratton MR, Gecz J, Zinn AR, "Refined mapping of X-linked reticulate pigmentary disorder and sequencing of candidate genes" Hum Genet, in press Spring 2008
Kublaoui BM, Gemelli T, Tolson KP, Wang Y, Zinn AR, "Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice" Mol Endocrinol, in press Spring 2008
SIGNIFICANT PUBLICATIONS
Holder J L, Butte N F, Zinn A R, "Profound obesity associated with a balanced translocation that disrupts the SIM1 gene" Hun Mol Gen, 9:101-108, 2000
Ross J L, Roeltgen D, Kushner H, Wei F, Zinn A R, "The Turner syndrome, associated neurocognitive phenotype maps to distal Xp" Am J Hum Genetics, 67:672-681, 2000
Holder Jr. JL et al., "Sim1 gene dosage modulates the homeostatic feeding response to increased dietary fat in mice" Am J Phys Endocrinol Metab, Spring 2004
Kublaoui BM, Holder JL Jr, Gemelli T, Zinn AR, "Sim1 haploinsufficiency impairs melanocortin-mediated anorexia and activation of paraventricular nucleus neurons" Mol Endocrinol, 20:2483-2492, Fall 2006
Kublaoui BM, Gemelli T, Tolson KP, Wang Y, Zinn AR, "Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice" Mol Endocrinol, in press Spring 2008
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