Table 4.

Mouse models (knockouts - KO or transgenic-TG, i.e., ubiquitous expression of the gene, unless specified) for intracrine enzymes.

Gene∧	Modification MGI ID$	Phenotype
SatAR	Null/KO1 MGI: 2388706	Endocrine (steroids) & reproductive endocrinology - abnormal endocrine organs (adrenal, ovaries, prostate, testis). - decreased steroids and increased adrenocorticotropin level. - adrenocortical insufficiency. - loss of negative feedback regulation at hypothalamic-pituitary levels.
		Additional Growth retardation neo/post natal lethality (incomplete penetrance). Reproductive system: abnormal uterus; incomplete spermatogenesis; abnormal genitalia.
CYP11A1	Null/KO2 MGI:5464022	Endocrine (steroids) and reproductive endocrinology - abnormal adrenal gland morphology. - increased circulating adrenocorticotropin level. - lack of steroid production. - decreased corticosterone and aldosterone levels.
	Null/KO3 MGI: 2183813	Additional Neonatal lethality (rescued by steroid supplementation); abnormal mitochondrion morphology; abnormal lipid level. Reproductive system: abnormal genitalia, prostate, testis morphology and spermatogenesis; Nervous system: abnormal adrenaline and noradrenaline level; abnormal food intake, hypoactivity; postnatal growth retardation.
CYP17A1	Null/KO4 MGI:3722780	Endocrine (steroids) & reproductive endocrinology - increased circulating cholesterol level. - decreased T level. - early reproductive senescence.
	Null/KO5 MGI:3047328 Null/KO MGI:5605834	Additional Homozygous embryonic lethality (Ed7, between implantation and somite formation). Reproductive system: abnormal sperm flagellum morphology/asthenozoospermia; reduced male fertility. Bone: abnormal bone structure, mineral content and density. Metabolism: increased total body fat; decreased lean body mass; increased circulating creatinine level; increased fasted circulating glucose level. Nervous system: abnormal sexual interaction.
CYP19A1	Null/KO6 MGI:2179439	Endocrine (steroids) and reproductive endocrinology - increased circulating cholesterol, T, DHT, FSH, LH and prolactin. - decreased circulating E2 level. - abnormal endometrium (thin, decreased uterus weight). - abnormal ovary (absence of follicles and corpus luteum, anovulation).
	Null/KO7 MGI:2154536 Null/KO8 MGI:2389548	Additional Reproductive system: ovary hemorrhage and cysts; increased seminal vesicle weight and abnormal seminiferous tubule epithelium and oligozoospermia; female infertility and reduced male fertility. Metabolism: increased fat; obesity and susceptibility to weight gain. Bone: decreased bone mineral density and bone mass; increased bone resorption, osteoclast cell number; abnormal compact and trabecular bone morphology. Metabolism: increased circulating glucose and triglyceride levels; impaired glucose tolerance; insulin resistance; hepatic steatosis; abnormal liver physiology. Nervous system: abnormal short term spatial reference memory; abnormal emotion/affect behavior; abnormal barbering behavior; increased grooming behavior; abnormal locomotor activation, bradykinesia; abnormal mating frequency.
17βHSD1	Null/KO9 MGI:5576042 and 3799948	Endocrine (steroids) & reproductive endocrinology - abnormal corpus luteum morphology and decreased number. - increased ovarian E1:E2 and A4:T ratios. - increased LH level. - reduced P level.
		Additional Increased circulating alkaline phosphatase level, pigmentation, abnormal retinal pigmentation, abnormal lens morphology, abnormal retina morphology, abnormal retinal pigmentation. Reproductive system: increased ovary weight; reduced female fertility. Metabolism: decreased circulating glucose level. Nervous system: abnormal behavior, response to light, sleep behavior, decreased exploration in new environment; abnormal motor coordination/balance.
17bHSD1	TG10	Reproductive endocrinology - female have increased T levels. - increased E1E2 conversion. - masculinization in females. - develop benign/malignant breast, ovarian and endometrial conditions.
17βHSD2	Null/KO11 MGI:3773836	No clear reproductive endocrinology phenotype Additional Heterozygous mice: growth retardation at birth ant postnatal; premature death; renal degeneration. Reproductive system: 70% embryonic lethality (Ed11.5) due to placental defects (homozygous); small and abnormal placenta morphology; Nervous system: brain phenotype with enlarged ventricles; abnormal cortex morphology; impaired balance, coordination, abnormal sleep pattern, megacephaly.
	TG12	Reproductive endocrinology - low T level.
		Additional Growth retardation; delayed eye opening; impaired retinoic signaling. Reproductive system: disrupted spermatogenesis. Bone: decreased bone formation (pre-pubertal age); decreased IGF-I and osteocalcin levels.
17βHSD4	Null/KO13	No clear reproductive endocrinology phenotype Additional Neonatal and postnatal lethality; postnatal growth retardation; abnormal mitochondrion morphology; abnormal bile salt level; hepatic steatosis. Reproductive system: abnormal testis and spermatid morphology; seminiferous tubule degeneration; small testis; abnormal gametogenesis; reduced male fertility. Nervous system: microgliosis; Purkinje cell degeneration; astrocytosis; axon degeneration; abnormal suckling behavior; increased anxiety-related response, tremors, ataxia, impaired coordination, hypoactivity, lethargy; abnormal gait. GIT: abnormal intestinal absorption. Metabolism: decreased body weight; abnormal lipid homeostasis and decreased fatty acid level.
17βHSD7	Null/KO14 MGI:3811923	Endocrine (steroids) Cholesterol biosynthesis.
	Null/KO15 MGI:4456868	Additional Decreased embryo size; embryo lethality due to heart malformations (Ed10.5); abnormal blood vessel and capillary morphology. Nervous system: brain malformations; forebrain hypoplasia; increased neural tube apoptosis.
17βHSD9	Null/KO16 MGI: 2446073 Null/KO17 MGI:2388375	No clear reproductive endocrinology phenotype Additional Visual defects; abnormal eye electrophysiology, delayed dark adaptation.
17βHSD10	Null/KO18	No clear reproductive endocrinology phenotype Additional Mitochondria dysfunction; reduced plasma glucose and increase insulin levels. Nervous system: neuronal damage.
	TG (brain specific)19	No clear reproductive endocrinology phenotype Additional Nervous system: Protect against ischemia, Parkinson, Alzheimer disease model
17βHSD11	Null/KO20 MGI:5581418	No clear reproductive endocrinology phenotype Additional Increased total circulating protein level. Nervous system: hyperactivity.
17βHSD12	Null/KO21	No clear reproductive endocrinology phenotype Additional Embryo lethality Ed 9.5; impaired organogenesis; reduced arachidonic acid synthesis. Reproductive system: ovarian dysfunction, fertility problems, smaller litters, significantly fewer numbers of ductal branches than wild type female mammary glands; ovulation problems. Nervous system: high embryo expression in neuronal structures.
17βHSD13	Null/KO22 MGI:5007180	No clear phenotype associated.
17βHSD14	Null/KO23 MGI:5007181	No clear reproductive endocrinology phenotype Additional Increased IgG2a level. Reproductive system: oligozoospermia, testis degeneration, male infertility. Nervous system: increased response to stress-induced hyperthermia.
17βHSD15	Null/KO24 MGI:3526658 & 3586379	No clear reproductive endocrinology phenotype Additional Abnormal eye electrophysiology, delayed dark adaptation
AKR1C3/ 17βHSD5*	Null/KO25 MGI:3527218	Reproductive endocrinology - long gestation, parturition failure. - increased levels of P. - prolonged estrous and diestrous.
	Null/KO26 MGI:3774264	Additional Small litter size, the number of pups, especially live pups, was markedly decreased hematopoietic system phenotype. Nervous system: Some behavioral phonotype,
SRD5A1	Null/KO27 MGI:1857454	Reproductive endocrinology - parturition defects, rescued by 3α-DIOL supplementation.
		Additional Decreased litter size; small prostate.
SRD5A2	Null/KO28 MGI:2178039	Reproductive endocrinology - T accumulation in reproductive tissues. - impaired androgen-dependent gene expression. - parturition defects, rescued by 3α-DIOL supplementation.
		Additional Decreased litter size; small prostate.
SRD5A3	Null/KO29 MGI:5520177	Mouse not thoroughly characterized Embryonic lethality, abnormal heart morphology, abnormal neural tube closure
SULT1E1	Null/KO30 MGI:3529586	Reproductive endocrinology - elevated circulating estrogen levels.
		Additional Disturbed platelet physiology. Reproductive system: leyding cell hyperplasia and abnormal morphology; abnormal testis morphology; abnormal placentation and amniotic fluid composition.
SULT2B1	Null/KO MGI:5432568 (unpublished)	Endocrine (steroids) disturbed cholesterol metabolism and levels.

^∧No report/references was found for 17βHSD3, 17βHSD6, 17βHSD8, 3βHSD1, 3βHSD2, DHRS11, STS, SULT2A1, SULT1A1.

^*The human AKR1C3/17βHSD5 KO refers to mice with disrupted AKR1C18, however, functional conservation between the four human AKR1Cs and the eight mouse AKR1Cs in unclear (Sudeshna et al., 2013).

^$Reference ID refers to the Mouse Genome Informatics (MGI; www.informatics.jax.org. Accessed on date: February 2018) (Blake et al., 2017).

¹Caron et al. (1997), ²Huang et al. (2012), ³Hu et al. (2002), ⁴Liu et al. (2005), ⁵Bair and Mellon (2004), ⁶Nemoto et al. (2000), ⁷ Fisher et al. (1998), ⁸Honda et al. (1998), ⁹Hakkarainen et al. (2015), ¹⁰Saloniemi et al. (2010) and Järvensivu et al. (2018), ¹¹Rantakari et al. (2008), ¹²Zhongyi et al. (2007), ¹³Baes et al. (2000), ¹⁴Shehu et al. (2008), ¹⁵Jokela et al. (2010), ¹⁶Shang et al. (2002), ¹⁷Driessen et al. (2000) and Sahu et al. (2015); ¹⁸Li et al. (2010) and Rauschenberger et al. (2010); ¹⁹Li et al. (2010); Rauschenberger et al. (2010), ²⁰Dickinson et al. (2016), ²¹Rantakari et al. (2010); Kemilainen et al. (2016); ²²Tang et al. (2010), ²³Tang et al. (2010), ²⁴Kim et al. (2005), ²⁵Piekorz et al. (2005), ²⁶Ishida et al. (2007), ²⁷Mahendroo et al. (1996), ²⁸Mahendroo et al. (2001), ²⁹Dickinson et al. (2016), ³⁰Qian et al. (2001) and Tong et al. (2005).