# Mouse Sbp2 deficiency models the multi-system syndrome of human SBP2 defects > **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $350,489 ## Abstract PROJECT SUMMARY/ABSTRACT The medical consequences of impaired selenoprotein synthesis became apparent with the identification by the PI of the first mutations in the selenocysteine insertion sequence binding protein 2 (SBP2) gene causing a syndrome of SBP2 deficiency. SBP2 is an essential factor required for the Sec incorporation and selenoprotein synthesis. Affected subjects present characteristic thyroid tests abnormalities that have not been identified in other inherited or acquired defects and have not been replicated by animal models targeting selenoprotein synthesis. Although the thyroid phenotype is presumed to be caused by abnormal function of the selenoenzymes deiodinases, the exact mechanisms responsible for this consistent pattern remain elusive. Other phenotypic components of this syndromic defect also reflect multiple selenoprotein deficiencies, manifested with growth delay, congenital myopathy, developmental delay, infertility, delayed puberty, complex immune deficits and metabolic parameters with increased insulin sensitivity. The only adult patient reported is 35 years old and has the most complex phenotype, manifesting most of the different abnormalities listed above. This raises concern for the possibility that the young patients known to harbor recessive SBP2 deficiency might manifest new health problems as they age. As many questions have been raised by the human phenotype of SBP2 deficiency, in-vivo studies in a model organism are required to fully assess the pathophysiology responsible for this pleiotropic phenotype. The current proposal addresses this need, using a mouse model of SBP2 deficiency generated by the PI. To bypass the early lethality of complete Sbp2 deficiency, a cre-estrogen receptor/loxP approach was employed to engineer induced mice Null/iCKO. Importantly, phenotypes of human SBP2 deficiency were replicated in the Sbp2 deficient mice. With this critical tool in hand this proposal aims to begin elucidate aspects of selenoprotein-mediated pathology by dissecting the pathognomonic thyroid phenotypes and the metabolic manifestations. To dissect the different components contributing to the unique serum thyroid function tests, components of the hypothalamic-pituitary-thyroid axis will be investigated in detail at baseline and in challenging conditions, such as exogenous thyroid hormone administration. Considering that certain selenoproteins act to promote adiposity and insulin resistance whereas others protect against it, the resulting metabolic phenotype of Sbp2 deficiency is the result of multi-organ contributions. Features of the metabolic phenotype will be investigated in Sbp2 deficient mice through detailed studies in metabolic tissues, metabolic parameters will be determined in mice studied in metabolic cages, at baseline and in challenging conditions when fed high fat diet. The results of the proposed studies will significantly advance our understanding of the role of SPB2 in TH homeostasis and cellular met... ## Key facts - **NIH application ID:** 9938543 - **Project number:** 5R01DK110322-05 - **Recipient organization:** UNIVERSITY OF CHICAGO - **Principal Investigator:** Alexandra Mihaela Dumitrescu - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $350,489 - **Award type:** 5 - **Project period:** 2016-07-01 → 2022-11-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9938543 ## Citation > US National Institutes of Health, RePORTER application 9938543, Mouse Sbp2 deficiency models the multi-system syndrome of human SBP2 defects (5R01DK110322-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9938543. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*