Funding outcome

Background: Osteoporosis and childhood disorders of bone health are frequently the result of altered calcium (Ca2+) homeostasis. Ca2+ balance is controlled by proteins in the kidneys and intestines that are important for its absorption, including Claudin-2, Claudin-12, and TRPV6. However, the exact roles of these proteins on bone health are not fully understood. Research Models: We will use genetically modified mice to study the effect of disrupting these proteins. Mice lacking Claudin-2, Claudin-12, and TRPV6 will be generated to help us understand how the failure of Ca2+-transport proteins affects bone health. Hypothesis: We believe that the loss of these 3 proteins will cause low Ca2+ levels in the blood. In response, the body will try to compensate by increasing hormones like parathyroid hormone and vitamin D. Despite these compensatory efforts, bone strength and structure will be negatively impacted. Research Aims: 1) Investigate how the loss of these proteins affects Ca2+ balance. 2) Determine how hormones change in response to low Ca2+ levels. 3) Examine the impact on bone health. 4) Analyze the possible compensation pathways in the kidneys and intestine. Methodology: We will measure Ca2+ levels in the blood and urine of control and triple knockout mice, track hormone changes, and use imaging techniques to assess bone health. Additionally, we will examine how the expression of Ca2+ transport genes is affected in compensation. Impact: This study will deepen our understanding of how Ca2+ transport disruptions contribute to bone diseases like osteoporosis. The findings could lead to better treatments for osteoporosis, a disorder that predominantly affects women.