All Phenotypes Ggt1<tm1Zuk> MGI Mouse

premature death ( J:34309 , J:77691 )

• most mice die between 10 and 18 weeks of age (J:34309)

• lethality rescued by administration of N-acetyl cysteine in drinking water starting at weaning (J:77691)

abnormal coat/hair pigmentation ( J:34309 )

diluted coat color ( J:34309 )

• agouti mice have a gray hue

• etiology: low levels of cysteine compromises phaeomelanin synthesis

abnormal postnatal growth/weight/body size ( J:34309 )

decreased body weight ( J:34309 )

• by 6 weeks of age, mice weigh about half the weight of normal siblings

disproportionate dwarf ( J:84348 )

postnatal growth retardation ( J:65574 )

• mice are growth retarded starting as early as 2 weeks of age

decreased cysteine level ( J:65574 )

• ovarian cysteine levels are significantly reduced at 13 weeks but not at 6 weeks of age

• testicular cysteine levels are significantly reduced at both 6 and 13 weeks of age

• however, cysteine levels are unchanged in the seminal vesicles

• also, glutathione (GSH) levels remain unchanged in the testes, ovaries, and seminal vesicles

decreased circulating cysteine level ( J:34309 )

• plasma cysteine levels are reduced by 80%

decreased circulating testosterone level ( J:65574 )

• serum testosterone levels are significantly low in males at 8 and 13 weeks of age

decreased circulating estradiol level ( J:65574 )

• at P42, serum estradiol levels are not detectable in females

decreased circulating follicle stimulating hormone level ( J:65574 )

• at 6-8 weeks of age, serum FSH levels are significantly reduced in males

• however, serum FSH levels are not suppressed in females

decreased circulating insulin-like growth factor I level ( J:65574 )

• at 6-8 weeks of age, serum IGF-I levels are undetectable in males

increased circulating growth hormone level ( J:65574 )

• at 6-8 weeks of age, males show a 25% increase in serum growth hormone level relative to wild-type controls

abnormal glucose homeostasis ( J:34309 )

abnormal lens morphology ( J:34309 )

cataract ( J:34309 , J:66279 )

• mice develop cataracts by 7 days (J:34309)

• severe cataracts develop by 3 weeks of age (J:66279)

• etiology: exposure to light, reduced lens GSH levels, and nutritional effects secondary to low cysteine levels (J:66279)

nuclear cataract ( J:66279 )

• nuclear opacities are evident by 1 week of age

abnormal long bone epiphyseal plate proliferative zone ( J:84348 )

• decreased growth plate

• etiology: proliferative defect of chondrocytes

decreased bone mass ( J:84348 )

• due to increased osteoclast number and activity

oocyte degeneration ( J:65574 )

• many more degenerating oocytes are observed at 10-11 weeks of age

oligozoospermia ( J:65574 )

• a massive reduction in epididymal sperm number is observed at 8 weeks of age

immotile sperm ( J:65574 )

• the few epididymal sperm present are completely immotile

seminal vesicle hypoplasia ( J:65574 )

• seminal vesicles are severely hypoplastic at 8 weeks of age

• administration of N-acetylcysteine (NAC) in the drinking water starting on P21 for 2 weeks restores seminal vesicle size to wild-type values

• NAC withdrawal causes a severe reduction in seminal vesicle size by 72 hr; by 10 days of NAC withdrawal, seminal vesicle size is reduced by ~60%

absent corpus luteum ( J:65574 )

• corpora lutea are absent at 10-11 weeks of age

absent tertiary ovarian follicles ( J:65574 )

• antral follicles are absent at 10-11 weeks of age

impaired ovarian folliculogenesis ( J:65574 )

• follicular growth is arrested at the secondary follicle stage

• follicular degeneration is apparent between 11 and 13 weeks of age

ovary hypoplasia ( J:65574 )

• ovaries are hypoplastic at 6 weeks of age

• administration of N-acetylcysteine in the drinking water starting on P21 for 2 weeks restores ovary size to wild-type values

small seminiferous tubules ( J:65574 )

• seminiferous tubule diameter is reduced at 8 weeks of age

• however, development of the spermatogenic and somatic cells of the testis is grossly normal

small testis ( J:65574 )

• testis size is significantly decreased at 8 weeks of age or earlier

• administration of N-acetylcysteine in the drinking water starting on P21 for 2 weeks restores testis size to wild-type values

decreased testis weight ( J:65574 )

• testis weight is significantly decreased at 8 and 13 weeks of age

uterus hypoplasia ( J:65574 )

• uteri are hypoplastic at 6 weeks of age

epididymis hypoplasia ( J:65574 )

• epididymis is severely hypoplastic at 8 weeks of age

• administration of N-acetylcysteine (NAC) in the drinking water starting on P21 for 2 weeks restores epididymis size to wild-type values

• NAC withdrawal causes a progressive moderate decrease in epididymal size

abnormal reproductive system development ( J:34309 )

• reproductive tracts of both females and males are hypoplastic

failure of superovulation ( J:65574 )

• at 21-23 days of age, immature females are insensitive to exogenous gonadotropin administration and fail to superovulate

absent estrous cycle ( J:65574 )

• female mice are not cycling

female infertility ( J:65574 )

• matings of female mice with wild-type control males do not result in any offspring over a period of 2 months, indicating female infertility

• however, continuously N-acetylcysteine-fed female mice are fertile and produce normal numbers of offspring when mated to wild-type control males

male infertility ( J:65574 )

• at 8 weeks of age, none of the males tested produced any offspring, indicating male infertility

• however, continuously N-acetylcysteine-fed male mice are fertile and produce normal numbers of offspring when mated to wild-type control females