Phenotypes for Cftr MGI:3689378 MGI Mouse

lung inflammation ( J:112450 )

• increased inflammatory response to chronic Pseudomonas aeruginosa infection, identical to that in Cftr^tm1Unc homozygotes

decreased respiratory epithelial chloride transmembrane transport ( J:112450 )

• after treatment with a chloride-depleted solution with amiloride and forskolin, the nasal potential difference (PD) was significantly different between control mice and homozygous mice

impaired sperm migration in female genital tract ( J:145380 )

• sperm transport within the mutant female reproductive system is significantly impaired: the average number of sperm found in mutant oviducts is only ~10% of wild-type

• however, no differences in capacitation of oviductal sperm are observed

increased susceptibility to bacterial infection induced morbidity/mortality ( J:112450 )

• reduced ability to respond to lung infection elicited with Pseudomonas aeruginosa- laden agarose beads

postnatal growth retardation ( J:112450 , J:145380 )

• weighed significantly less (P 0.05) than homozygote wild-type controls at 7, 14, and 21 days of age (J:112450)

• at 6-8 and 14-16 weeks of age, total body weight is reduced by only 15% and 12%, respectively, thus not explaining the larger differences noted in average weight of reproductive organs (~50% and 36%, respectively) (J:145380)

intestinal obstruction ( J:112450 )

• develop intestinal blockage when fed a normal (solid) diet

lung inflammation ( J:112450 )

• increased inflammatory response to chronic Pseudomonas aeruginosa infection, identical to that in Cftr^tm1Unc homozygotes

increased susceptibility to bacterial infection induced morbidity/mortality ( J:112450 )

• reduced ability to respond to lung infection elicited with Pseudomonas aeruginosa- laden agarose beads

impaired sperm migration in female genital tract ( J:145380 )

• sperm transport within the mutant female reproductive system is significantly impaired: the average number of sperm found in mutant oviducts is only ~10% of wild-type

• however, no differences in capacitation of oviductal sperm are observed

decreased corpora lutea number ( J:145380 )

• female homozygotes show an average of 1.5 +/- 2.0 corpora lutea per ovary vs 9.3 +/- 1.4 in wild-type females, even though other follicle stages are present

small ovary ( J:145380 )

• at 7 weeks of age, female homozygotes display smaller ovaries than wild-type females

decreased ovary weight ( J:145380 )

• at 6-8 and 14-16 weeks of age, the average weight of mutant ovaries is reduced by 50% and 36%, respectively, relative to that of wild-type ovaries

• however, mutant ovarian weight is restored to wild-type values after superovulation

abnormal uterine cervix morphology ( J:145380 )

• only 1 of 15 female homozygotes showed cervical mucus accumulation with no other physical signs of obstruction in the uterus

small uterus ( J:145380 )

• at 7 weeks of age, female homozygotes display smaller uteri than wild-type females

decreased uterus weight ( J:145380 )

• at 6-8 and 14-16 weeks of age, the average weight of mutant uteri is reduced by 56% and 36%, respectively, relative to that of wild-type uteri

• however, mutant uterus weight is restored to wild-type values after superovulation

thin uterus ( J:145380 )

• mutant uteri are thinner than wild-type

delayed sexual maturation ( J:145380 )

• female homozygotes display a delayed onset of puberty relative to wild-type controls

decreased ovulation rate ( J:145380 )

• female homozygotes display reduced oocyte ovulation rates relative to wild-type females

• however, normal ovulation rates are observed after induction of superovulation with exogenous hormone (PMSG + hCG) injections

absent estrous cycle ( J:145380 )

• unlike wild-type females, 22.2% of 14-16-wk-old mutant females never enter estrus but are constantly in diestrus

prolonged estrous cycle ( J:145380 )

• at 14-16 weeks of age, female homozygotes that display at least one estrous cycle show half as many cycles as wild-type females, resulting in a 2-fold increase in average cycle length

reduced female fertility ( J:145380 )

• female homozygotes exhibit reduced fertility with significantly fewer numbers of litters and smaller litter sizes relative to wild-type females

• 35.7% of female homozygotes are unable to give birth over a 5-month mating period

• following induction of superovulation, only 1 of 10 mutant females that displayed vaginal plugs gave birth, but that female did give birth to 20 pups

decreased litter size ( J:145380 )

• female homozygotes show a significant decrease in average number of pups per litter relative to wild-type females (3.81 +/- 1.43 vs 6.56 +/- 2.36, respectively)

impaired fertilization ( J:145380 )

• at 48 hrs after hCG treatment, 98.4% of mutant oocytes remain unfertilized, whereas the majority of embryos from superovulated wild-type females are found at the 2- to 4-cell stages

• however, no significant differences in in vitro fertilization rates are observed, suggesting that decreased in vivo fertilization is more likely due to inadequate fluid control in the reproductive tract, resulting in decreased sperm number in the oviduct