Analysis Tools
limbs/digits/tail
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• in hindlimb, digit I was homeotically transformed into digit II
• less frequent than in hindlimb, only 5% of animals displayed defects in forelimb, thus incompelete penetrance, digit I was homeotically transformed into digit II
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• in hindlimb, a subset of animals were missing digit I
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polydactyly
(
J:62547
)
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• incomplete penetrance, in hindlimb, a subset of animals had an extra digit, which morphologically resembled digit V
• less frequent than in hindlimb, only 5% of animals displayed defects in forelimb, thus incompelete penetrance, an extra digit was present, which morphologically resembled digit V
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• homeotic transformation of the cuneiforme 1 to the naviculare bone (38%) or to the cuboid bone (42%)
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• in 90% of animals the talus was homeotically transformed into a calcenous
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• less frequent than in hindlimb, only 5% of animals displayed morphological defects in forelimb
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• failed to fuse with tibia
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absent fibula
(
J:62547
)
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• 16% of animals
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• thickened fibula in 32% of animals
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• failed to fuse with fibula
• 38% of animals had tibias that were transformed into fibula-like structures
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• 52% had duplicated or absent patella
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• 36% had short hindlimbs
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• bony outgrowths of metatarsal region seen in 69% of animals
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• 15% of animals showed complete fusion of metatarsal region
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• loss in number of caudal vertebrae, resulting in shortening of tail
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short tail
(
J:62547
)
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• due to loss of caudal vertebrae and fusion of cartilage between vertebrae
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kinked tail
(
J:62547
)
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• due to loss of caudal vertebrae and fusion of cartilage between vertebrae
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skeleton
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• homeotic transformation of the cuneiforme 1 to the naviculare bone (38%) or to the cuboid bone (42%)
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• in 90% of animals the talus was homeotically transformed into a calcenous
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• failed to fuse with tibia
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absent fibula
(
J:62547
)
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• 16% of animals
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• thickened fibula in 32% of animals
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• failed to fuse with fibula
• 38% of animals had tibias that were transformed into fibula-like structures
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• 52% had duplicated or absent patella
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• bony outgrowths of metatarsal region seen in 69% of animals
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• 15% of animals showed complete fusion of metatarsal region
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• loss in number of caudal vertebrae, resulting in shortening of tail
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• malformed with holes and fissures present
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• 70% of animals had an extra pair of ribs associated with an extra thoracic vertebra
• the extra pair of ribs was attached to the sternum
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• 14 thoracic vertebrae were present in 70% of the mice, rather than the normal 13 found in control animals
• the extra segment was associated with an extra pair of ribs, which were attached to the sternum
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• transformation of T8 into more anterior thoracic segments
• shift of transitional vertebrae from T10 to T11, so that T10 resembles T9
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• transformation of L1 into more posterior thoracic segments
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• S2 resembles S1
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reproductive system
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• transplantation experiments showed that mutant spermatogonia obtained at 3-4 months of age are unable to repopulate germ cell-depleted recipient testis, indicating a depletion of spermatogonial stem cells in adult mutant males
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• at 1 and 2 weeks after birth, mutant testes have more seminiferous tubules containing cleaved caspase 3-positive apoptotic cells than wild-type testes
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• at 6 months of age, male homozygotes show significantly low numbers of viable, actively progressive motile sperm relative to wild-type controls
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• by 3 months of age, a large portion of mutant seminiferous tubules have degenerated and no longer contain spermatogonia or differentiating spermatocytes
• at 3 months, some tubules appear normal while others contain only Sertoli cells; occasionally, degenerated tubules contain only elongated spermatids
• no obvious tubule degeneration is noted until 2 weeks of age, despite decreasing numbers of proliferating spermatogonia at this early age
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• adult mutant testes display expansion of the Leydig cells surrounding the degenerating seminiferous tubules
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small testis
(
J:91129
)
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• at 3 months of age, mutant testes are significantly smaller than wild-type
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• impaired spermatogenesis due to progressive loss of spermatogonia with age
• although spermatogenesis occurs in some tubules, leading to production of elongated spermatids, earlier stages of subsequent rounds of the cycling seminiferous epithelium are lost
• microarray analysis of mutant spermatogonia isolated prior to testis degeneration indicated alterations in the expression profile of spermatogenesis-associated genes
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• at 6 months of age, male homozygotes show a significant reduction in epididymal spermatozoa number and sperm count relative to wild-type controls
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• at 3 months of age, many degenerating tubules lack proliferating (PCNA-positive) spermatogonia but retain p27-positive Sertoli cells along the basement membrane
• a significant and progressive decrease in the overall number of proliferative spermatogonia is first evident at 2 weeks of age
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endocrine/exocrine glands
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• by 3 months of age, a large portion of mutant seminiferous tubules have degenerated and no longer contain spermatogonia or differentiating spermatocytes
• at 3 months, some tubules appear normal while others contain only Sertoli cells; occasionally, degenerated tubules contain only elongated spermatids
• no obvious tubule degeneration is noted until 2 weeks of age, despite decreasing numbers of proliferating spermatogonia at this early age
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• adult mutant testes display expansion of the Leydig cells surrounding the degenerating seminiferous tubules
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small testis
(
J:91129
)
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• at 3 months of age, mutant testes are significantly smaller than wild-type
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homeostasis/metabolism
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• adult male homozygotes (<6 months old) show increased serum levels of active testosterone relative to wild-type controls
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cellular
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• at 6 months of age, male homozygotes show a significant reduction in epididymal spermatozoa number and sperm count relative to wild-type controls
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• transplantation experiments showed that mutant spermatogonia obtained at 3-4 months of age are unable to repopulate germ cell-depleted recipient testis, indicating a depletion of spermatogonial stem cells in adult mutant males
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• at 1 and 2 weeks after birth, mutant testes have more seminiferous tubules containing cleaved caspase 3-positive apoptotic cells than wild-type testes
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• at 6 months of age, male homozygotes show significantly low numbers of viable, actively progressive motile sperm relative to wild-type controls
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• at 3 months of age, many degenerating tubules lack proliferating (PCNA-positive) spermatogonia but retain p27-positive Sertoli cells along the basement membrane
• a significant and progressive decrease in the overall number of proliferative spermatogonia is first evident at 2 weeks of age
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hematopoietic system
| N |
• no defects in myeloid hematopoiesis
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