Analysis Tools
muscle
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• the terminal cisternae of the sarcoplasmic reticulum is slightly swollen compared to in wild-type muscles
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• after 18 months, 30% of mice exhibit accelerated muscle wasting compared with wild-type mice
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• muscle phenotypes worsen with age
• in myotubes treated with thapsigargin, the magnitude of calcium transient is reduced and the duration of the decaying phase is increased compared to in similarly treated wild-type myotubes
• store operated calcium entry is blunted compared to in wild-type muscles
• ionomycin-mobilized calcium is decreased compared to in wild-type muscle
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• the kinetics of a single tetanic contraction of the soleus muscle is altered and the plateau phase of the contraction is not well maintained unlike wild-type muscle
• Tmax of the soleus muscles is reduced 15% compared with wild-type muscle
• the normalized force versus frequency relationship is shifted right compared with wild-type muscles
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• male mice exhibit increased end diastolic diameter and cardiac index compared with wild-type mice
• however, female mice exhibit normal heart physiology
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• the force-generating capacity of the extensor digitorum longus is decreased 60% compared with wild-type cells
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• in the absence of ryanodine, high K+-evoked smooth muscle contraction of the vas deferens is significantly lower than in wild-type controls
• addition of ryanodine fails to result in a further decrease in muscle contraction of the vas deferens, unlike in wild-type controls
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• muscle relaxation profiles are prolonged compared to in wild-type mice
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• mice exhibit decreased running time when run to exhaustion compared with wild-type mice
• repeated exposure to electrical stimulations results in increased resting baseline force, decreased maximum tetanic force, and non-responsiveness to subsequent stimulations unlike similarly treated wild-type muscle
• the soleus muscle exhibits greater fatigue and reduced recovery compared with wild-type muscle
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cardiovascular system
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• posterior wall thickness is decreased in male mice compared with wild-type mice
• however, female mice exhibit normal heart morphology
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• male mice exhibit increased end diastolic diameter and cardiac index compared with wild-type mice
• however, female mice exhibit normal heart physiology
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behavior/neurological
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• on a rotarod or inclined screen
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• mice exhibit decreased running time when run to exhaustion compared with wild-type mice
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homeostasis/metabolism
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• mice exhibit decreased running time when run to exhaustion compared with wild-type mice
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• intracellular calcium ion homeostasis in the testes and epididymis is impaired
• intracellular Ca2+ concentration ([Ca2+]i) is significantly increased in spermatogonial cells but significantly decreased in mature epididymal sperm relative to wild-type controls
• mRNA levels of calcium channel receptors Itpr1, Itpr2 and Ryr3 are significantly decreased in mature sperm
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reproductive system
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• female fertility appears unaffected
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• total number of sperm collected from both sides of the testes, epididymis, and vas deferens is significantly lower than in age-matched wild-type males
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• proportion of apoptotic spermatogenic cells is significantly higher than in wild-type testes, as determined by a TUNEL assay
• annexin V/PI staining and flow cytometry analysis of spermatozoa indicated a significantly higher ratio of apoptosis than in wild-type spermatozoa
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• proportion of motile sperm cells is decreased by half relative to that in age-matched wild-type males
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small testis
(
J:267733
)
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• at 6 weeks of age, testis/body weight ratio is significantly lower than in wild-type controls
• difference in testis/body weight ratio is slightly increased at 12 weeks of age
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• at 8 weeks of age, testis histology showed abnormal structures of seminiferous tubules and fewer spermatogonia
• mRNA expression levels of several genes involved in spermatogenesis -- Rad23b, Adad1, Zfp35, Tsnaxip1, Spag16, Hmgb2, and Hook1 -- are significantly reduced in testes, indicating impaired spermatogenesis
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• ~28% of mature sperm from both the epididymis and vas deferens show abnormal morphology versus only 12% of wild-type sperm
• TEM analysis showed that membranes of epididymal sperm tails are expanded and creased
• however, no obvious loss of microtubule structure is observed
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• hairpin structures are observed in the sperm midpiece
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• hairpin structures are observed in the sperm principal piece
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• hairpin structures are observed in the sperm tail
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• truncated sperm flagella are observed
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• abnormal sperm heads and abnormal junctions between sperm heads and midpieces are observed
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• when mated with adult males, half of wild-type female mice do not become pregnant over a 3-month breeding period
• however, average litter size is normal in those wild-type females that become pregnant
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• in vitro fertilization ability of cauda epididymal sperm is significantly decreased
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• in the absence of calcium ionophore A23187 treatment, the proportion of capacitated sperm undergoing acrosome reaction is significantly lower than in wild-type sperm
• after treatment with A23187 for only 5 min, less than 10% of sperm undergo the acrosome reaction versus ~50% in wild-type controls
• however, no difference in the acrosome reaction is observed after 20 min of stimulation with A23187
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• in vitro fertilization analysis of cauda epididymal sperm using eggs from superovulated wild-type females showed a significant decrease in the rate of 2-cell embryo formation relative to wild-type sperm (25.3% versus 81.3%)
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endocrine/exocrine glands
small testis
(
J:267733
)
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• at 6 weeks of age, testis/body weight ratio is significantly lower than in wild-type controls
• difference in testis/body weight ratio is slightly increased at 12 weeks of age
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cellular
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• ~28% of mature sperm from both the epididymis and vas deferens show abnormal morphology versus only 12% of wild-type sperm
• TEM analysis showed that membranes of epididymal sperm tails are expanded and creased
• however, no obvious loss of microtubule structure is observed
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• hairpin structures are observed in the sperm midpiece
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• hairpin structures are observed in the sperm principal piece
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• hairpin structures are observed in the sperm tail
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• truncated sperm flagella are observed
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• abnormal sperm heads and abnormal junctions between sperm heads and midpieces are observed
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• total number of sperm collected from both sides of the testes, epididymis, and vas deferens is significantly lower than in age-matched wild-type males
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• proportion of apoptotic spermatogenic cells is significantly higher than in wild-type testes, as determined by a TUNEL assay
• annexin V/PI staining and flow cytometry analysis of spermatozoa indicated a significantly higher ratio of apoptosis than in wild-type spermatozoa
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• proportion of motile sperm cells is decreased by half relative to that in age-matched wild-type males
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adipose tissue
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• mice are overtly fatter than wild-type controls
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growth/size/body
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• mice are overtly fatter than wild-type controls
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