Table 3.

Trsp conditional knockout mouse models.

Targeted Tissue or Organ 1	Main Findings Regarding Role of Selenoproteins in Genetically-Altered Mice, Relative to Control Mice in the Study	Cre Promoter
Endothelial cells	Endothelial cell development/function: embryonic lethal. 14.5 d.p.c. embryos were smaller, more fragile, had poorly or under-developed vascular systems, limbs, head, and tail [133].	TieTek2-Cre
Heart & Skeletal Muscle	Heart disease prevention: mice died from acute myocardial failure 12 days after birth.	MCK-Cre
Kidney	No increase in oxidative stress or nephropathy found in podocytes of selenoprotein-deficient mice [141].	NPHS2-Cre
Liver	Liver function: severe hepatocellular degeneration—mice died between 1 and 3 months of age [82]. SELENOP and GPX3 were reduced in serum and kidney, supporting a selenium-transport role for liver-derived SELENOP [140]. Enhanced expression of phase II response genes compensated for loss of hepatic Trsp [145]. Mice used as controls to monitor selenium pools in kidney due to reduction of GPX3 imported from liver [146]. Secisbp2 gene inactivation was less detrimental than Trsp inactivation [147].	Alb-Cre
Macrophages	Immune function: increased oxidative stress and expression of cytoprotective antioxidant and detoxification genes, accumulation of ROS levels, and impaired invasiveness. Altered expression of ECM and fibrosis-associated genes [148]. Balance of pro- and anti-inflammatory oxylipids during inflammation [149]. Selenoproteins protect mice from chemically-induced colitis by alleviating inflammation [150]. Role in epigenetic modulation of pro-inflammatory genes [151]. When infected with N. brasiliensis, selenium-supplemented KO mice showed a complete abrogation in M2-marker expression with a significant increase in intestinal worms and fecal eggs [152].	LysM-Cre
Mammary glands	First Trsp conditional KO mouse, providing an important tool for elucidating the role of selenoproteins in health and development [123]. MMTV-Cre mice treated with DMBA had significantly more tumors, suggesting that selenoproteins protect against carcinogen-induced mammary cancer [153].	MMTV-Cre; Wap-Cre
Neurons	Neuronal function: enhanced neuronal excitation followed by neurodegeneration of hippocampus. Cerebellar hypoplasia associated with degeneration of Purkinje and granule cells. Cerebellar interneurons essentially absent [139]. Selenoproteins required in post-mitotic neurons of the developing cerebellum [154].	Tal-Cre; CamK-Cre
Osteo-chondroprogenitor	Kashin–Beck disease model: mice had post-natal growth retardation, chondrodysplasia, chondronecrosis, and delayed skeletal ossification characteristic of Kashin–Beck disease [134].	Col2a1-Cre
Prostate	Mice developed PIN-like lesions and microinvasive carcinoma by 24 weeks, which were associated with loss of basement membrane, increased cell cycle, and apoptotic activity [143].	PB-Cre4
Skin	Role in skin and hair follicle development: runt phenotype, premature death, alopecia with flaky and fragile skin, epidermal hyperplasia with disturbed hair cycle, and an early regression of hair follicles [135].	K14-Cre
T-cells	Immune function: reduction of mature T cells and a defect in T-cell-dependent antibody response. Antioxidant hyperproduction and suppression of T cell proliferation in response to T cell receptor stimulation [137].	LCK-Cre
Thyroid	Mice lacking selenoproteins in thyrocytes showed increased oxidative stress in thyroid. Gross morphology remained intact for at least 6 months. Thyroid hormone levels remained normal in knockout mice; thyrotropin levels moderately elevated [142].	Pax8-Cre; Tg-CreER

¹ Target organs/tissues in alphabetical order. Abbreviations: days-post-coitum (d.p.c.); 7,12-dimethylbenz[a]anthracene (DMBA); extracellular matrix (ECM); mouse mammary tumor virus (MMTV); prostatic intraepithelial neoplasia (PIN).