Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes.
The hypothalamic-pituitary axes are the coordinating centers for multiple endocrine gland functions and physiological processes. Defects in the hypothalamus or pituitary gland can cause reduced growth and severe short stature, affecting approximately 1 in 4000 children, and a large percentage of cases of pituitary hormone deficiencies do not have an identified genetic cause. SOX21 is a protein that regulates hair, neural, and trophoblast stem cell differentiation. Mice lacking Sox21 have reduced growth, but the etiology of this growth defect has not been described. We studied the expression of Sox21 in hypothalamic-pituitary development and examined multiple endocrine axes in these mice. We find no evidence of reduced intrauterine growth, food intake, or physical activity, but there is evidence for increased energy expenditure in mutants. In addition, despite changes in pituitary hormone expression, hypothalamic-pituitary axes appear to be functional. Therefore, SOX21 variants may be a cause of non-endocrine short stature in humans.
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
Leonard Y M
LYM
Cheung
Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Hideyuki
H
Okano
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA. Electronic address: scamper@med.umich.edu.
Sally A
SA
Camper
D000818:Animals; D000831:Animals, Newborn; D001481:Basal Metabolism; D001835:Body Weight; D004027:Diencephalon / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D013006:Growth Hormone / Q000378:metabolism; D048788:Growth and Development; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D009928:Organ Specificity; D010902:Pituitary Gland / Q000378:metabolism*; D055749:SOXB2 Transcription Factors / Q000235:genetics*; D013974:Thyroxine / Q000097:blood
D055749:SOXB2 Transcription Factors; D013006:Growth Hormone; D013974:Thyroxine
Hypothalamus; Metabolism; Pituitary; SOX21; SoxB1