disabling the erα or erβ. the following sections are an extensive though partial/incomplete list of deficits observed in erko mice. females estradiol and lh levels are dramatically elevated due to loss of negative feedback by estradiol on the hpg axis. fsh levels, in contrast, are normal. testosterone levels are also substantially elevated. prolactin levels are decreased by 5-fold, which is due to a loss of its estradiol-induced secretion from the anterior pituitary. the uterus and endometrium show hypoplasia and hypotrophy, respectively, and the vagina is atrophic. the oviduct is normal. the ovary is normal until sexual maturity, at which point there is complete anovulation and the ovaries become enlarged, hemorrhagic, and cystic. because there is complete anovulation, female αerko mice are infertile. the ovarian phenotype closely resembles that of polycystic ovary syndrome (pcos) in humans. it is caused by chronic exposure to abnormally high levels of lh. by 18 months of age, there is a 30 to 40% incidence of ovarian tumors. the mammary gland is normal until puberty, at which point there is a complete absence of pubertal development and the gland remains in a prepubertal state. body weight and body fat are increased. there are signs of insulin resistance, as in pcos in humans. due to the substantially elevated testosterone levels, there is hyperandrogenism, including masculinization of the preputial glands. in addition, female αerko mice exhibit behavior that is similar to that of males in terms of parental, aggressive, and sexual activities. there is a complete lack of sexual receptivity, measured as lordosis behavior. there are significant deficits in parental behavior, including a tendency toward infanticide, and aggressive behavior is increased. males lh and testosterone levels are both increased 2-fold due to loss of negative feedback by estradiol on the hpg axis. the testes develop relatively normally initially, but are slightly smaller than normal and possess various defects. by 20 weeks, the weights of the testes, epididymis, and vas deferens are significantly decreased relative to those of normal mice. however, there is a severe testicular phenotype with age, such that the testes are completely atrophied by 150 days of age. also, the testes show leydig cell hyperplasia, which is due to the increased levels of lh and intratesticular testosterone. further, there is a greater incidence of cryptorchidism (undescended/retracted testes). there is complete infertility, which is due both to testicular defects and to severely compromised normal sexual behavior (see below). males can produce viable sperm, but there are severe deficits in both spermatogenesis and sperm function, the latter rendering produced sperm ineffective. sperm counts are significantly reduced, at 55% of those of normal mice, and further diminish with age, at 13% of those of normal mice by 16 weeks of age. there are deficits in sperm motility, an increased incidence of sperm defects (specifically, sperm heads separated from the flagellum (tail)), and a complete inability of sperm to fertilize oocytes (assessed in vitro). there are no obvious abnormalities in the male accessory glands, including the prostate gland, bulbourethral glands, coagulating gland, and seminal vesicles. however, there is a significant increase in weight of the seminal vesicles/coagulating gland that becomes more apparent with age, which is likely due to elevated testosterone levels. aggressive behavior is dramatically reduced, whereas parental behavior, in terms of infanticide, is relatively normal. there is little effect on sexual behavior in terms of mounting and sexual attraction to females. however, there is an almost complete lack of intromission and ejaculation, in spite of the relatively normal mounting rate. this contributes to infertility. females the uterus, vagina, and oviducts are normal. the ovary is normal prior to puberty, and there is still no gross aberrant phenotype during adulthood. however, there is partial anovulation and subfertility, which is due to ovarian defects, namely compromised follicular maturation via loss of estradiol signaling in ovarian granulosa cells. the mammary gland appears to be normal. body weight and fat distribution appear to be normal. increased anxiety-like behavior is seen. in addition, the antidepressant-like effects of exogenous estradiol in the forced swim test are lost. males fertility is full and normal, with a lack of relevant phenotypes observed. the male accessory glands, including the prostate gland, bulbourethral glands, coagulating gland, and seminal vesicles, all seem to be normal. however, there is an increased incidence of prostate hyperplasia with age. body weight and fat distribution appear to be normal. there is a lack of grossly apparent behavioral phenotypes, including in regards to sexual behavior. however, increased aggressive behavior is observed. gperko mice gper knockout mice have also been generated, and exhibit obesity, cardiovascular dysfunction, insulin resistance, glucose intolerance, differences in mammary carcinogenesis and metastasis, and differences in central nervous system function. androgen insensitivity syndrome main article: androgen insensitivity syndrome in contrast to eis, androgen insensitivity syndrome (ais), a condition in which the androgen receptor (ar) is defective, is relatively common. this can be explained by the genetics of each syndrome. ais is an x-linked recessive condition and thus carried over, by females, into future generations (although the most severe form, complete androgen insensitivity syndrome (cais), results in sterility, and hence cannot be passed on to offspring). eis is not compatible with reproduction, thus each occurrence in humans would have to be a de novo mutation and is not transmitted to offspring.