reproductive system
N |
• mutant males show normal secondary sex organ morphology and are capable of strong penile erections
|
• by 6 weeks some tubules show selective loss of spermatogonia
(J:100645)
• although normal at P4, GFRA1-positive spermatogonial stem cell (SSC) density is decreased 17%, 32%, and 95% at P8, P12, and P28, respectively
(J:135433)
• no GFRA1-positive SSCs are detected in mutant males at later stages (P36 and P44)
(J:135433)
|
• at P44, TUNEL staining of mutant seminiferous tubules indicates an increase in apoptosis of round spermatids, but not other germ cells, relative to wild-type controls
|
• at P44, sperm from the cauda epididymis of mutant males are less motile than wild-type sperm (7.0 3.2% vs 41.0 4.9%, respectively)
|
small testis
(
J:100645
)
|
• although normal at P4, mutant testis weights are 27% smaller than wild-type controls by P8
• testis weight reduction becomes more pronounced (41% to 75%) at later ages (P36 and P56) when progressive loss of spermatogenesis occurs
• by P90, mutant testis weights are reduced by 86% relative to wild-type controls, reflecting total loss of spermatogenesis by this age
• in mutant males, the ratio of body weight to testis weight begins to increase as these mice lose spermatogenesis; by P90, the ratio of body weight to testis weight is comparable to that seen at P4
|
• the initial wave of spermatogenesis is normal but by 6 weeks tubules show selective loss of spermatogonia only or a combined loss of preleptotene and pachytene spermatocytes
• progressive loss of spermatogenesis culminates in a loss of all germ cells and a Sertoli cell-only phenotype by 10 weeks of age
|
azoospermia
(
J:100645
)
• by 10 weeks of age most tubules lack germ cells
|
• at P44-P56, the average concentration of sperm in the cauda epididymis of mutant males is reduced by ~7-fold relative to wild-type controls
|
• by 6 weeks some tubules show a combined loss of preleptotene and pachytene spermatocytes
|
• at 4 weeks of age, spermatogonial proliferation is severely reduced and there is a failure to maintain spermatogonia; however levels of testosterone and follicle-stimulating hormone are normal and no increase in apoptosis is detected
|
• at P44, decrease in sperm concentration in mutant males is partly due to impaired spermiation and subsequent phagocytosis of elongated (step 16) spermatids by Sertoli cells
• numerous sloughed round bodies and spermatids are present in the lumen
|
(J:100645)
• unlike wild-type males, 35- to 56-day-old mutant males are infertile as assessed by natural breeding, artificial insemination, and in vitro fertilization, although motile sperm are present in mutant epididymides during this time
(J:135433)
|
endocrine/exocrine glands
small testis
(
J:100645
)
|
• although normal at P4, mutant testis weights are 27% smaller than wild-type controls by P8
• testis weight reduction becomes more pronounced (41% to 75%) at later ages (P36 and P56) when progressive loss of spermatogenesis occurs
• by P90, mutant testis weights are reduced by 86% relative to wild-type controls, reflecting total loss of spermatogenesis by this age
• in mutant males, the ratio of body weight to testis weight begins to increase as these mice lose spermatogenesis; by P90, the ratio of body weight to testis weight is comparable to that seen at P4
|
growth/size/body
• male mutants display a 60% reduction in the mRNA level of the vomeronasal receptor V1RC3, responsible for sensing female pheromones
|
• male homozygotes display decreased body weights relative to wild-type controls at all ages from P8 to P90 days
• differences in body weights range from 12% to 31% and are significant at all ages except for days P4, P12, P24, and P28
|
behavior/neurological
• mutant males fail to produce copulation plugs and thus impregnate wild-type females
• only 1 of 5 mutant males show a response following placement in a cage with estrous urine, suggesting an impaired ability to sense and/or respond to female pheromones that may contribute to the lack of mating
|
nervous system
• male mutants display a 60% reduction in the mRNA level of the vomeronasal receptor V1RC3, responsible for sensing female pheromones
|
respiratory system
• male mutants display a 60% reduction in the mRNA level of the vomeronasal receptor V1RC3, responsible for sensing female pheromones
|
craniofacial
• male mutants display a 60% reduction in the mRNA level of the vomeronasal receptor V1RC3, responsible for sensing female pheromones
|
cellular
azoospermia
(
J:100645
)
• by 10 weeks of age most tubules lack germ cells
|
• at P44-P56, the average concentration of sperm in the cauda epididymis of mutant males is reduced by ~7-fold relative to wild-type controls
|
• by 6 weeks some tubules show a combined loss of preleptotene and pachytene spermatocytes
|
• by 6 weeks some tubules show selective loss of spermatogonia
(J:100645)
• although normal at P4, GFRA1-positive spermatogonial stem cell (SSC) density is decreased 17%, 32%, and 95% at P8, P12, and P28, respectively
(J:135433)
• no GFRA1-positive SSCs are detected in mutant males at later stages (P36 and P44)
(J:135433)
|
• at P44, TUNEL staining of mutant seminiferous tubules indicates an increase in apoptosis of round spermatids, but not other germ cells, relative to wild-type controls
|
• at P44, sperm from the cauda epididymis of mutant males are less motile than wild-type sperm (7.0 3.2% vs 41.0 4.9%, respectively)
|
• at 4 weeks of age, spermatogonial proliferation is severely reduced and there is a failure to maintain spermatogonia; however levels of testosterone and follicle-stimulating hormone are normal and no increase in apoptosis is detected
|