All Phenotypes Olfm1<tm1.1Lex> MGI Mouse

• at birth, females show ~5% less body weight than wild-type females

• females show significantly lower body weight than wild-type or heterozygous controls from birth to adulthood, with ~17%-25% less body weight from 1 to 8 weeks of age

decreased gonadotropin-releasing hormone neuron number ( J:226939 )

• females show a 13% reduction in the total number of hypothalamic GnRH neurons in the preoptic area and anterior hypothalamus relative to wild-type controls

• however, basal serum LH levels and GnRH-induced LH levels are normal in 3-mo-old females at diestrus

decreased cerebral infarct size ( J:118333 )

• following transient middle cerebral artery occlusion, cortical infarct size is significantly smaller than in wild-type males

abnormal accessory olfactory bulb morphology ( J:226939 )

• upon male urine stimulation for 90 min, young adult virgin females show a 41% reduction in Fos-positive cells in the mitral cell layer of accessory olfactory bulb relative to wild-type controls

absent corpus luteum ( J:226939 )

• corpora lutea are never observed in young females, indicating defective ovulation

delayed sexual maturation ( J:226939 )

• upon exposure to male soiled bedding, females are unresponsive to the effects of male odor stimulation on several parameters of pubertal development and estrous cyclicity

delayed vaginal opening ( J:226939 )

• vaginal opening is delayed by ~4 days relative to wild-type or heterozygous females

• exposure to male soiled bedding fails to accelerate vaginal opening in 3-k-old females, unlike in wild-type controls

decreased ovulation rate ( J:226939 )

• among 7 females with no implantation sites, 3 had no oocytes or embryos flushed from the reproductive tract, one had 1 oocyte flushed from the uterus, and 3 females had 1-3 oocytes flushed from the oviduct

• ovulation rate is significantly decreased in young adult virgin females

• superovulation (eCG alone) restores the ovulation rate in all juvenile (21- to 23-day-old) females tested, suggesting a functional HPG axis

decreased superovulation rate ( J:226939 )

• after superovulation (eCG + hCG), juvenile 3-wk-old females show a ~27% reduction in the average number of cumulus oocyte complexes (COCs) relative to wild-type controls

• after superovulation with eCG alone, juvenile females show a ~36% reduction in the average number of COCs relative to wild-type controls

abnormal estrous cycle ( J:226939 )

• 20% (4 of 20) young adult virgin females tested showed an estrus stage but none of them had a complete estrous cycle during the 5 days before or after exposure to male soiled bedding

• those 4 females with estrus stage either remained in estrus stage or had only estrus stage and metestrus stage

delayed embryo implantation ( J:226939 )

• 2 of 9 plugged females tested showed faint implantation sites on gestational day 4.5, indicating delayed embryo implantation

failure of embryo implantation ( J:226939 )

• 7 of the 9 plugged females tested showed no implantation sites on gestational day 4.5

female infertility ( J:226939 )

• most females are infertile

reduced female fertility ( J:118333 , J:226939 )

• homozygous breeding pairs do not breed well; however, the colony can be maintained by crossing homozygous males to heterozygous females, indicating reduced female fertility (J:118333)

• over a 6-mo fertility test, only 1 of eight (12.5%) females ever delivered pups, with a total of 4 litters and an average litter size of only 3.3 +/- 1.5 per litter (J:226939)

• during a 4-mo cohabitation with wild-type studs, only 14.3% (1 of 7) plugged females delivered pups versus 83.3% (10 of 12) of plugged wild-type females (J:226939)

• superovulation (eCG + and hCG) restores fertility in 2- to 4-month-old females to wild-type levels in terms of delivery rate, litter size and gestational period (J:226939)

• reduced fertility is most likely a secondary effect of impaired olfaction (J:226939)

abnormal sexual interaction ( J:226939 )

• females rarely mate and those that mate rarely become pregnant

• during a 4-mo cohabitation with wild-type studs, the mating rate of young adult females is 46.7% (7 of 15) versus 100% in wild-type females

• 5 of 7 plugged females mated over a markedly prolonged time period after cohabitation with a median of 49 days, whereas most plugged wild-type females (11 of 12) mated within 4 days of cohabitation with a median of 2 days

• overall mating activity of young females is >50-fold lower than in wild-type females

abnormal copulatory plug deposition ( J:226939 )

• females are rarely plugged; some females get plugged after an extended cohabitation period

• first plug latency is dramatically prolonged with a median of 49 days versus 2 days in wild-type females

• superovulation (eCG + and hCG) completely restores mating activity in all 2- to 4-mo-old females, with a copulation plug found the first night of cohabitation

failure of copulatory plug deposition ( J:226939 )

• in a 1-month mating test using only one female and one stud male per cage, none of the 6 females tested got plugged

impaired olfaction ( J:226939 )

• young adult virgin females lack estrous cyclicity and do not respond to the effects of male odor stimulation, indicating that olfaction defects affect their estrous cyclicity and fertility

increased circulating follicle stimulating hormone level ( J:226939 )

• at diestrus, basal serum FSH levels are significantly increased in young adult (3-mo-old) virgin females