mortality/aging
• homozygous mice at weaning stage found at a significantly lower rate (73/519) than expected Mendelian ratio (130/519) from heterozygous mutant intercross
|
embryo
• severely reduced
• lacks large islands of glycogen cells
• thin at E12.5
|
• severely reduced
• lack large islands of glycogen cells
• thin at E12.5
|
• near absence of large islands of glycogen cells in the spongiotrophoblast layer
• no massive invasion of glycogen cells in the decidual layer
|
• reduced volume without disruption in structure
|
• at E16.5
|
growth/size/body
• adult mice are 20% smaller than wild-type littermates
|
• through adulthood
|
• reduction in 4-week old male body weight of around 20% compared to wild-type or Ptp4a1 homozygous knockout
|
• at E16.5
|
reproductive system
N |
• males show no significant differences in Sertoli cell number, prostate and seminal vesicle size, or sperm motility relative to wild-type controls
(J:209512)
• normal Sertoli cell numbers in 3-months old testis, as determined by vimentin staining
(J:250112)
• normal numbers of undifferentiated spermatogonia in 3-months old testis, as determined by Zbtb16 (PLZF) staining
(J:250112)
|
• at 2 weeks of age, the number of Kit-positive cells (differentiating spermatogonia and primary spermatocytes) per seminiferous tubule is significantly reduced, while the number of PLZF-positive undifferentiated spermatogonia is normal
(J:209512)
• 30 +/- 4% reduction in differentiating spermatogonia and primary spermatocytes, as determined by Kit staining
(J:250112)
|
• male germ cells isolated from 3-month-old testes show a 1.6-fold increase in PTEN protein level leading to a reduction in both basal and Stem Cell Factor (SCF)-induced Akt phosphorylation
|
• number of apoptotic cells is 6-fold higher at 2 weeks and at 3 months and 9-fold higher at 6 months of age, as shown by cleaved PARP1 staining
(J:209512)
• TUNEL staining confirmed that germ cell apoptosis is increased at 2 weeks of age
(J:209512)
• 3-fold increase in number of apoptotic cells in 3-months old testis according to cleaved-PARP1 staining
(J:250112)
|
• severely reduced
• lacks large islands of glycogen cells
• thin at E12.5
|
• abnormal clusters of germ cells are found in the lumen of seminiferous tubules at 3 months and, more frequently, at 6 months of age; most of these are apoptotic cells, as shown by cleaved PARP1 staining
(J:209512)
• seminiferous tubules are either totally or partially devoid of germ cells at 6 months
(J:209512)
• however, average Sertoli cell number per tubule is normal, as shown by vimentin labeling
(J:209512)
• empty space where certain cell types are lost
(J:250112)
|
• seminiferous epithelium thickness is significantly reduced at 2 weeks of age
|
• diameter of seminiferous tubules is reduced by ~20% at 3 months of age
(J:209512)
• tubule diameter is reduced as early as at 2 weeks of age
(J:209512)
• diameter reduced by 21 +/- 6%
(J:250112)
|
• testes are markedly smaller at 3 months of age
(J:209512)
• reduction in testis weight of 43 +/- 8% compared to wild-type
(J:250112)
|
• ~30% reduction in testis/body weight ratio at 3 months of age
(J:209512)
• reduction in testis weight of 43 +/- 8% compared to wild-type
(J:250112)
• reduction in testis/body weight ratio (normalized body weight) of 33 +/- 16% compared to wild-type
(J:250112)
|
• males develop testicular hypotrophy
|
• spermatogenesis is impaired largely, if not entirely, due to blockage of Kit-PI3K-Akt signaling, as a result of elevated PTEN expression
|
• epididymis contains significantly fewer spermatozoa than wild-type, esp. at 6 months of age
(J:209512)
• 54 +/- 18% reduction in sperm count in epididymis of 3-months old males compared to wild-type
(J:250112)
|
• caudal epididymis shows paucity of spermatozoa along with numerous ectopically released germ cells in the epididymal lumen at 6 months of age
(J:209512)
• numerous round-shaped cells released into cauda epididymis
(J:250112)
|
• after mating with wild-type virgin females for 6 consecutive days, average litter size derived from 3- or 6-month-old males is smaller than that from age-matched wild-type males
|
• males exhibit full penetrance of sterility after 9 months of age
|
• despite a normal sexual drive, males show a progressive decline in fertility, first evident at 3 months of age
• by 6 months of age, only 20% of plugged females become pregnant versus 71% of females plugged by wild-type males
|
immune system
cellular
• at 2 weeks of age, the number of Kit-positive cells (differentiating spermatogonia and primary spermatocytes) per seminiferous tubule is significantly reduced, while the number of PLZF-positive undifferentiated spermatogonia is normal
(J:209512)
• 30 +/- 4% reduction in differentiating spermatogonia and primary spermatocytes, as determined by Kit staining
(J:250112)
|
• epididymis contains significantly fewer spermatozoa than wild-type, esp. at 6 months of age
(J:209512)
• 54 +/- 18% reduction in sperm count in epididymis of 3-months old males compared to wild-type
(J:250112)
|
• in the spongiotrophoblast at E12.5
|
• male germ cells isolated from 3-month-old testes show a 1.6-fold increase in PTEN protein level leading to a reduction in both basal and Stem Cell Factor (SCF)-induced Akt phosphorylation
|
• number of apoptotic cells is 6-fold higher at 2 weeks and at 3 months and 9-fold higher at 6 months of age, as shown by cleaved PARP1 staining
(J:209512)
• TUNEL staining confirmed that germ cell apoptosis is increased at 2 weeks of age
(J:209512)
• 3-fold increase in number of apoptotic cells in 3-months old testis according to cleaved-PARP1 staining
(J:250112)
|
endocrine/exocrine glands
• abnormal clusters of germ cells are found in the lumen of seminiferous tubules at 3 months and, more frequently, at 6 months of age; most of these are apoptotic cells, as shown by cleaved PARP1 staining
(J:209512)
• seminiferous tubules are either totally or partially devoid of germ cells at 6 months
(J:209512)
• however, average Sertoli cell number per tubule is normal, as shown by vimentin labeling
(J:209512)
• empty space where certain cell types are lost
(J:250112)
|
• seminiferous epithelium thickness is significantly reduced at 2 weeks of age
|
• diameter of seminiferous tubules is reduced by ~20% at 3 months of age
(J:209512)
• tubule diameter is reduced as early as at 2 weeks of age
(J:209512)
• diameter reduced by 21 +/- 6%
(J:250112)
|
• testes are markedly smaller at 3 months of age
(J:209512)
• reduction in testis weight of 43 +/- 8% compared to wild-type
(J:250112)
|
• ~30% reduction in testis/body weight ratio at 3 months of age
(J:209512)
• reduction in testis weight of 43 +/- 8% compared to wild-type
(J:250112)
• reduction in testis/body weight ratio (normalized body weight) of 33 +/- 16% compared to wild-type
(J:250112)
|
• males develop testicular hypotrophy
|
hematopoietic system
homeostasis/metabolism
N |
• males show no significant differences in serum testosterone levels relative to wild-type males
|