Analysis Tools
mortality/aging
|
• most mutant females exhibit premature reproductive senescence and support only 3-4 pregnancies during the first few months of a 9-month period
|
cellular
 |
• reduced number or absence of spermatids at 8 weeks of age
|
azoospermia
(
J:39356
)
|
|
• absence of spermatozoa in the epididymis at 8 weeks of age
|
behavior/neurological
polyphagia
(
J:96351
)
|
• at 12-19 weeks of age, male (but not female) homozygotes exhibit significantly increased food intake over wild-type males
|
|
• at 5-10 weeks of age, preobese male homozygotes display significantly reduced voluntary running wheel activity relative to wild-type males
• similarly, at 7 and 11 weeks of age, female homozygotes exhibit significantly reduced voluntary running wheel activity, regardless of the stage of the estrous cycle
• however, no differences in circadian rhythm, balance, or learning of motor tasks are observed
|
|
|
• male mice did not copulate
|
 |
• both young and aged female homozygotes show at least a 50% reduction in hormone-stimulated sexual behavior as measured by their lordosis quotient
|
digestive/alimentary system
|
• slight reduction in the distance from the penis to the anus
|
endocrine/exocrine glands
| N |
• serum levels of growth hormone (GH) and luteinizing hormone (LH) were normal in male mice
|
|
|
• preputial glands were either small or absent
|
|
|
• convoluted
|
|
|
• arrested at the early stages of antral formation
|
small ovary
(
J:39356
)
|
|
• females raised in the absence of males exhibited small and pale ovaries
• size reduction was not apparent until after 4.5 weeks of age
|
|
|
• rudimentary lumens
|
|
|
• only remnants of the tubules remained at 32 weeks of age
|
|
|
• reduced number of Leydig cells at 32 weeks of age
|
small testis
(
J:39356
)
|
|
• significant reduction after 8 weeks of age, though apparent at 4.5 weeks of age
• testicular tissue was largely replaced by a capsule of fat at 32 weeks of age
|
growth/size/body
|
• progressive adult-onset obesity
• adipose tissue accumulation in the peri-renal, peri-gonadal, and subcutaneous areas of the body
|
|
• at 4-7 weeks of age, male homozygotes show a significant weight reduction relative to wild-type males; however, starting at 10-12 weeks, male homozygotes show a progressive increase in body weight that is equivalent to 14% and 33% over wild-type at the age of 25 and 52 weeks, respectively
• unlike males, female homozygotes exhibit normal body weights at young ages (5-6 weeks), but become significantly heavier than wild-type females by 7 weeks of age
• with the exception of female homozygotes which show increased lean body mass at >52 weeks of age, increased body weight is due to increased body fat, and not due to overall increases in lean mass, body size, or length
• adult-onset obesity is preceded by reduced voluntary activity; increased food intake and decreased body temperature appear to play a role in maintaining a higher body weight with increasing age
|
homeostasis/metabolism
| N |
• blood glucose, insulin, and blood cholesterol levels were within normal ranges
|
|
• reduced in males observed at 8 to 20 weeks of age
|
|
• 4-fold decrease in male mice
|
|
• at >52 weeks of age (but not earlier), female homozygotes exhibit a 1.335 C reduction in core body temperature relative to wild-type females
• in contrast, male homozygotes show no significant differences in body temperature at any age relative to wild-type males
|
renal/urinary system
|
|
• preputial glands were either small or absent
|
small penis
(
J:39356
)
|
|
|
reproductive system
|
|
• reduced number or absence of spermatids at 8 weeks of age
|
|
• slight reduction in the distance from the penis to the anus
|
|
|
• preputial glands were either small or absent
|
|
|
• convoluted
|
|
|
• arrested at the early stages of antral formation
|
|
|
• rudimentary lumens
|
|
|
• only remnants of the tubules remained at 32 weeks of age
|
|
|
• reduced number of Leydig cells at 32 weeks of age
|
|
• most mutant females exhibit premature reproductive senescence and support only 3-4 pregnancies during the first few months of a 9-month period
|
small penis
(
J:39356
)
|
|
|
small uterus
(
J:39356
)
|
|
• females raised in the absence of males exhibited small uteri with threadlike oviducts
• size reduction was not apparent until after 4.5 weeks of age
|
azoospermia
(
J:39356
)
|
|
• absence of spermatozoa in the epididymis at 8 weeks of age
|
|
|
• reduced in size
|
small gonad
(
J:39356
)
|
• both male and female homozygotes are hypogonadal with an ~50% reduction or more in gonad size relative to wild-type littermates
|
small ovary
(
J:39356
)
|
|
• females raised in the absence of males exhibited small and pale ovaries
• size reduction was not apparent until after 4.5 weeks of age
|
small testis
(
J:39356
)
|
|
• significant reduction after 8 weeks of age, though apparent at 4.5 weeks of age
• testicular tissue was largely replaced by a capsule of fat at 32 weeks of age
|
|
|
• in response to exogenous hormones, young female homozygotes ovulate the same number of oocytes as wild-type females; however, the number of oocytes released by aged female homozygotes is reduced by >50%, indicating an age-associated reduction in oocytes
• notably, oocytes from female homozygotes are equally competent for in vitro fertilization assays relative to oocytes from similarly aged wild-type and heterozygous females
|
|
|
• 5-month-old female homozygotes display abnormal estrous cycles characterized by a severely truncated estrus and a prolonged diestrus and proestrus
|
short estrus
(
J:101925
)
|
|
• severely truncated
|
|
|
• females raised in the presence of males were fertile, whereas females raised under "male free" conditions had fewer litters
(J:39356)
• in the presence of wild-type or heterozygous males, young female homozygotes (8-12 week-old) can become pregnant and carry litters to full term with no differences in ovulation or litter size relative to age-matched heterozygous and wild-type females
(J:101925)
• however, unlike wild-type females in which fertility averages 8-12 months with ~1 pregnancy per month, mutant females show premature reproductive senescence with most females supporting only 3 to 4 pregnancies during the first few months of a 9-month period
(J:101925)
|
|
• females raised under "male free" conditions gave birth to smaller litters
|
adipose tissue
|
• at 12-19 weeks (or earlier), male homozygotes show normal percent body fat relative to wild-type males; however, male homozygotes average 11.7% (at 20-51 weeks) and 14.7% (at >52 weeks) more body fat than wild-type males
• unlike males, female homozygotes exhibit a trend toward increased body fat by 7 weeks of age with significantly increased body fat at 12-19 weeks; female homozygotes average 15.2% (at 20-51 weeks) and 14.9% (at >52 weeks) more fat than wild-type females
|
integument
|
|
• preputial glands were either small or absent
|
