Analysis Tools
mortality/aging
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• 80% die within 48 hours of birth
• survival is enhanced by paring down the litter sizes shortly after birth
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renal/urinary system
| N |
• kidney weights and numbers of glomeruli are normal
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• significantly reduced glomerular filtration rate in anesthetized and conscious homozygotes, accompanied by decreased K+ excretion
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homeostasis/metabolism
| N |
• normal basal values of blood gases, electrolytes, hematocrit, hemoglobin, plasma glucose, urine pH and osmolarity, with no proteinuria, normal circadian rhythms, and normal mean arterial blood pressure in freely moving, conscious mice
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• although some homozygotes have normal plasma creatinine levels, many have elevated plasma creatinine
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• approximately half normal levels
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growth/size/body
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• mutants are initially smaller than wild-type littermates but catch up after 3 months of age
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• the homozygotes that are carefully raised to adults become obese with a body weight of 44.3g versus 34.1g in wild-type siblings
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reproductive system
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• male homozygotes show a significant reduction of sperm motility relative to wild-type controls
• the percentage of mutant spermatozoa recovered from the swimming-up procedure is reduced by 80%
• however, no significant differences in spermatogenesis, sperm morphology or epididymal sperm count are observed, and testicular function appears unaffected
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• mutant sperm are unable to efficiently penetrate the oocyte vestments, due to abnormal flagellar movements, altered or untimely acrosome reactions, or both
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• homozygous matings do not produce any litters, even though males exhibit normal mountings and anogenital sniffing behavior when placed with females and females show plugs, indicating that vomeronasal organ responses are intact
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• mating of male homozygotes with fertile female controls over a period of 6 months revealed a significant reduction in litter size relative to similar mating of male heterozygotes
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• male homozygotes are subfertile with only 3 of 11 males producing offspring over a period of 6 months
• the 3 males that produced offspring generated only one litter each, even after mating with several females for >6 months
• however, sexual mounting behavior is present and vaginal plugs can be detected in wild-type females housed with homozygous mutant males
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• interestingly, untreated mutant spermatozoa show a significant increase in spontaneous acrosome reactions relative to untreated wild-type spermatozoa
• however, no significant differences in acrosome reactions are observed between mutant and wild-type sperm following treatment with the calcium ionophore A23187
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• mutant spermatozoa exhibit a 90% reduction in their capacity to fertilize wild-type eggs in vitro
• incubation of mutant spermatozoa with the cumulus-oocyte complex shows that the initial sperm egg interactions are normal
• the in vitro fertilizing capacity of mutant sperm is restored after removal of the zona pellucida
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taste/olfaction
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• mutants cannot detect some odorants, including isoamyl acetate, isomethone, citralva, lilial, geraniol, and isovaleric acid
• mutants can detect odorants such as ethyl propionate, ethyl acetate, ethyl vanillin, dimethyl pyrazine, butanone, and heptanone, however these odorants do not elicit an electro-olfactogram response in main olfactory bulb, indicating that mutants can detect odorants with the vomeronasal organ but not with the main olfactory bulb
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• odorant-evoked electrophysiological responses to both cAMP- and IP3-stimulating odors (2-hexylpyridine, isomenthone, citralva, lilial, triethylamine, isovaleric acid, and pyrazine) are ablated in the olfactory epithelium at P1 and 16 weeks of age
• mutants are unable to detect odorants in the sand-buried food test
• in an odorant-associated passive avoidance learning test, mutants do not exhibit a strong aversion to citralva or lilial as seen in wild-type
• however passive avoidance learning is normal, indicating that mutants do not have a general defect in fear-associate learning and memory
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nervous system
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• disorganized glomeruli in the main olfactory bulb
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• disorganization of axonal projections from olfactory sensory neurons into the glomerular layer
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cellular
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• male homozygotes show a significant reduction of sperm motility relative to wild-type controls
• the percentage of mutant spermatozoa recovered from the swimming-up procedure is reduced by 80%
• however, no significant differences in spermatogenesis, sperm morphology or epididymal sperm count are observed, and testicular function appears unaffected
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