Analysis Tools
reproductive system
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• although mutant preovulatory follicles do form at 48 hrs after PMSG treatment, they fail to display normal cumulus mucification at 10 hrs after induction of ovulation by hCG injection
• only faint hyaluronan staining is detected at 10 hrs after hCG injection, suggesting that mutant cumulus cells synthesize hyaluronan but are unable to organize it into an extracellular matrix
• after ovulation (13.5 hrs after hCG injection), cumulus cell-oocyte complexes (COCs) from control females show normal cumulus expansion, while most oocytes from homozygotes lack a cumulus layer, and are either completely nude or weakly associated with a loose network of granulosa/cumulus cells
• in vitro, mutant COCs obtained from PMSG-primed female homozygotes also fail to expand upon stimulation with dibutyryl cyclic AMP or epidermal growth factor (EGF), and shed most of their cumulus cells
• impaired cumulus matrix formation is due to the absence of covalent complexes between hyaluronan and the heavy chains of the inter-alpha-trypsin inhibitor family
• notably, recombinant TNFAIP6 catalyzes the covalent transfer of heavy chains to hyaluronan in a cell-free system, restores the expansion of mutant COCs in vitro, and rescues fertility in female homozygotes
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• after superovulation with consecutive injections of PMSG and hCG, the average number of oocytes recovered from the oviducts of female homozygotes (14 +/- 2) is significantly lower than that from wild-type (29 +/- 10) or heterozygous littermates (32 +/- 12)
• however, 12-wk-old female homozygotes appear to be able to ovulate under normal endocrine conditions, as indicated by the presence of corpora lutea
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• female homozygotes are sterile as a result of impaired cumulus matrix formation
• in contrast, both female heterozygotes and male homozygotes are fertile
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• in vivo, oocytes from superovulated female homozygotes mated with wild-type males fail to reach the two-cell stage
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endocrine/exocrine glands
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• impaired cumulus matrix formation is due to the absence of covalent complexes between hyaluronan and the heavy chains of the inter-alpha-trypsin inhibitor family
• although mutant preovulatory follicles do form at 48 hrs after PMSG treatment, they fail to display normal cumulus mucification at 10 hrs after induction of ovulation by hCG injection
• only faint hyaluronan staining is detected at 10 hrs after hCG injection, suggesting that mutant cumulus cells synthesize hyaluronan but are unable to organize it into an extracellular matrix
• after ovulation (13.5 hrs after hCG injection), cumulus cell-oocyte complexes (COCs) from control females show normal cumulus expansion, while most oocytes from homozygotes lack a cumulus layer, and are either completely nude or weakly associated with a loose network of granulosa/cumulus cells
• in vitro, mutant COCs obtained from PMSG-primed female homozygotes also fail to expand upon stimulation with dibutyryl cyclic AMP or epidermal growth factor (EGF), and shed most of their cumulus cells
• notably, recombinant TNFAIP6 catalyzes the covalent transfer of heavy chains to hyaluronan in a cell-free system, restores the expansion of mutant COCs in vitro, and rescues fertility in female homozygotes
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immune system
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• following OVA sensitization and aerosol challenge, mutants exhibit reduced airway inflammation, with reduced total leukocytes, airway eosinophils and macrophages
• however, humoral and cellular Th2 responses are normal
• reduction in pulmonary hyaluronan deposition following OVA aerosol challenge in OVA-immunized mice during induction of allergic pulmonary inflammation
• bronchoalveolar lavage hyaluronan levels in OVA/alum-immunized mice are reduced by about 30%
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respiratory system
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• mutants are resistant to the induction of airway hyperresponsiveness and show improved lung mechanics in response to metacholine challenge
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