Sox21 deletion in mice causes postnatal growth deficiency without physiological disruption of hypothalamic-pituitary endocrine axes

Abstract

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.

Single cell transcriptome analysis of developing arcuate nucleus neurons uncovers their key developmental regulators

“…4), and therefore Tbx3 may also control the development of Agrp Sst -neurons. Sox21-deficine mice showed enhanced energy expenditure 34 , and it will be interesting to investigate whether this phenotype involves the specific enrichment of the transcription factor Sox21 in our scRNA-seq dataset for developing Agrp-neurons and Pomc-neurons (Fig. 4), both of which control energy expenditure.…”

SOX21 Ensures Rostral Forebrain Identity by Suppression of WNT8B during Neural Regionalization of Human Embryonic Stem Cells

“…In addition to the rostral forebrain, SOX21 proteins were also detected in NPCs treated with 1.0–4.0 μM CT, suggesting that SOX21 has other functions in neural differentiation of hESCs and might act through different mechanisms. Sox21 KO mice are born normally, although they display cyclic alopecia and postnatal growth deficiency (Cheung et al., 2017, Kiso et al., 2009). This relatively minor phenotype could be explained by the functional redundancy among members of the Sox family, as they display overlaps of expression domains in the developing neural tissue (Uchikawa et al., 2011).…”

Whole‐genome SNP markers reveal conservation status, signatures of selection, and introgression in Chinese Laiwu pigs

“…plays an important role in formation of a diverse subset of skeletal joints (Clendenning & Mortlock, 2012). Mice lacking SOX21 was with reduced growth, and SOX21 variants may be a cause of nonendocrine short stature in human (Cheung, Okano, & Camper, 2017).…”