Project Number: 6250-51000-048-00
Start Date: May 21, 2004
End Date: Mar 30, 2009
1) Use generated LF knockout mice (LFKO) and two novel genetic mouse models that direct overexpression of LF to the small or large intestine, respectively, using intestinal-specific promoters. These unique gain-of-function transgenic mice will be used to investigate the effects of LF on iron homeostasis and host protection in the intestine of post weaning and adult mice thus eliminating any confounding factors in milk that may mask the functional properties(s) of LF during the suckling period. 2) Use mice that carry targeted inactivating germline mutations in the genes for IRS-1 or IRS-2 in combination with mammary tissue transplantation and primary cell culture approaches to determine the importance of activation of these signaling proteins in mammary cells to milk synthesis and/or mammary cell survival. 3) By testing if there is a finite period during early life when the infant maximally utilizes protein for growth and that failure to provide sufficient protein during this period results not only in short-and long-term growth deficits but also suboptimal neurodevelopment and by defining the period of maximum protein utilization for growth and the impact of size for gestational age as well as formula-feeding vs. breast-feeding on this period will be defined. 4) Perform a series of experiments of obese pregnant women and underweight teenagers in Houston and in underweight and normal weight adult women in India to test a series of hypotheses. 5) Develop a micronutrient-rich, energy-dense ready-to-use food and compare it to a fish-fortified porridge as a complementary food in 6-18 month old children. The quantity and quality of consumed breast milk will be measured and children will be followed longitudinally. The role of asymptomatic intestinal malabsorption in zinc homeostasis will be investigated in 3-5 year old children, using site specific gastrointestinal sugar absorption tests and zinc stable isotope techniques. 6) Analyze the chromatin structure and by analysis of transgenic mice harboring large BAC based transgenes with deletions or mutations of evolutionary conserved regions. 7) Methionine requirements that maintain nutritional balance and glutathione synthesis rates in health adolescent children will be studied through using intravenous indicator amino acid oxidation and balance technique.