Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hat1tm1.1Mrpa mutation
(0 available);
any
Hat1 mutation
(42 available)
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cellular
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• MEFs exhibit mitochondria with disorganized cristae that have an open structure
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• MEFs exhibit defective enlarged mitochondria
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• when incubated in glucosefree media supplemented with galactose over a 5day period, MEFs grow poorly on galactose whereas wildtype MEFs show a >20fold increase in cell proliferation by day 5
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• in culture, primary mouse embryonic fibroblasts (MEFs) show significant levels of senescence at passage 1 (~5%) that increase to ~35% by passage 7 and accumulate high levels of p21
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• MEFs exhibit a marked increase in DNA doublestrand breaks, as measured by comet assays
• untreated MEFs show an ~5-fold increase in the % of gammaH2AX+ cells relative to wild-type MEFs
• however, after incubation with antioxidant Nacetylcysteine (NAC), % of gammaH2AX+ cells is comparable to that in NAC-treated wild-type MEFs
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• MEFs show loss of mitochondrial membrane potential, as measured by fluorescence microscopy after JC1 staining: MEFs emit largely green fluorescence indicative of mitochondrial depolarization, whereas wild-type MEFs are predominantly red
• MEFs show a lower basal oxygen consumption rate (OCR) and a decreased maximal respiratory capacity
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• MEFs exhibit an ~2-fold increase in basal levels of reactive oxygen species (ROS) relative to wild-type MEFs
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hat1tm1.1Mrpa mutation
(0 available);
any
Hat1 mutation
(42 available)
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Skeletal defects in Hat1tm1.1Mrpa/Hat1tm1.1Mrpa mice
mortality/aging
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• mice either are born dead or die shortly after birth
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• mice either are born dead or die shortly after birth
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• fewer than expected mice are born
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respiratory system
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• the nasal passage is often missing, often overgrown with bone, in some mice
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• mice exhibit immature fetal lungs as determined by more cells per alveolar septum, vascularity, aerated lung tissue and septum thickness compared with wild-type mice
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• increased cell proliferation at E11.5 and in neonates
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• increased cell proliferation of lung interstitial cells at E11.5 and in neonates
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skeleton
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• fused into a single bone in some neonates
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• degenerate near the base of the spinal column
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• with reduced cartilage staining in the skull
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cellular
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• moderate accumulation of mouse embryonic fibroblasts in the G2/M
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• in mouse embryonic fibroblasts
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growth/size/body
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• the nasal passage is often missing, often overgrown with bone, in some mice
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craniofacial
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• fused into a single bone in some neonates
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• the nasal passage is often missing, often overgrown with bone, in some mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hat1tm1.1Mrpa mutation
(0 available);
any
Hat1 mutation
(42 available)
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mortality/aging
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• mice exhibit an average lifespan of 69.1 weeks; over a period of 120 weeks, 92% of mice died versus only 9% of wild-type controls
• ~40% of mice die spontaneously (cause indeterminate due to tissue lysis)
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• mice exhibit an array of phenotypes that are consistent with earlyonset aging
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growth/size/body
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• body size is reduced at birth; however, body size is normalized by 5 weeks of age
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• mice surviving to 80 weeks show a marked decrease in body weight
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• mice begin to exhibit weight loss after 40 weeks of age
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skeleton
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• 14.6% of mice exhibit lordokyphosis at the time of death
• 5.2% of mice exhibit lordokyphosis plus tumors at the time of death
• 8.3% of mice exhibit lordokyphosis plus hindlimb paralysis at the time of death
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adipose tissue
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• all mice sacrificed between 54 and 80 weeks of age exhibit an almost complete lack of subcutaneous fat tissue
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• 1 of 3 mice sacrificed between 54 and 80 weeks of age show visceral fat depletion
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• mice exhibit a trend towards decreased total body fat, as measured by EchoMRI
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• adipocytes are significantly smaller, indicating fat depletion
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muscle
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• at 54 weeks of age, quadriceps muscles show a significant loss of muscle mass
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• 5.2% of mice exhibit muscle degeneration/atrophy at the time of death
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• 2 of 3 mice sacrificed between 54 and 80 weeks of age show moderate skeletal muscle vacuolation (degeneration)
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• 5.2% of mice exhibit muscle degeneration/atrophy at the time of death
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• at 54 weeks of age, quadriceps muscles show increased mRNA levels of muscle atrophy markers Fbxo32 (F-box protein 32, aka MAFbx) and Trim63 (tripartite motif-containing 63, aka MuRF1)
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neoplasm
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• 8.3% of mice exhibit tumors at the time of death; tumors are found primarily in the liver, spleen, and kidney
• 5.2% of mice exhibit lordokyphosis plus tumors at the time of death
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• 50% of mice sacrificed between 54 and 80 weeks of age show histiocytic sarcoma in the liver while 33% of mice show histiocytic sarcoma in spleen
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behavior/neurological
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• 6.25% of mice exhibit hindlimb paralysis at the time of death
• 8.3% of mice exhibit lordokyphosis plus hindlimb paralysis at the time of death
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cardiovascular system
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• 1 of 3 mice sacrificed between 54 and 80 weeks of age show interventricular septum degeneration
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integument
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• all mice sacrificed between 54 and 80 weeks of age exhibit an almost complete lack of subcutaneous fat tissue
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cellular
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• in culture, primary mouse embryonic fibroblasts (MEFs) undergo early senescence and accumulate high levels of p21
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• MEFs exhibit a modest but statistically significant increase in DNA doublestrand breaks, as measured by comet assays
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• MEFs exhibit an ~2-fold increase in basal levels of reactive oxygen species (ROS) relative to wild-type MEFs
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homeostasis/metabolism
liver/biliary system
renal/urinary system
Analysis Tools