Analysis Tools
mortality/aging
|
• mutant mice die beginning at 8 weeks of age, with most dying at 10-12 weeks, and none living past 14 weeks
|
growth/size/body
|
• mutant mice cease to gain weight at one month of age and eventually weigh less than half as much as age-matched controls
|
nervous system
|
• in mutant mice end-plate area increases several-fold between postnatal day P6 and P50 but the number of Btx binding sites does not increase at all
• mutant endplates have significantly fewer AChRs than control endplates by approximately P10, and by 8 weeks of age, when mutant mice were beginning to die, the endplates have only 5% of control AChR numbers, distributed over 50-60% of the control area
• at P24, AChRs at mutant endplates are concentrated in patches or islands, separated by relatively receptor-poor regions of membrane, with no consistent correspondence seen between these patches and either junctional folds or presynaptic active zones; AChR-rich and AChR-poor areas were both present beneath single terminal boutons, and the synaptic cleft was no wider in AChR-poor than in AChR-rich areas
• several synaptic molecules showed a patchy distribution within mutant endplates, closely matching that of AChRs, including rapsyn and utrophin, erbB4 and MuSK, while other molecules were homogeneously
distributed within mutant endplates, extending over both AChR-rich and AChR-poor patches, including AChE, agrin and GalNAc-terminated glycoconjugates recognized by the lectin VVA-B4
• during postnatal development transition from simple endplate plaques to more complex shapes occurred during the same period in both mutants and controls, and mature endplates of both genotypes appeared equally intricate
• synapse elimination is not affected; levels of multiple innervation were similar in mutant and control muscles, falling from approx. 70% at P5 to <10% at P10
• the molecular maturation of the postsynaptic apparatus occurs in the mutant mice as assessed by the appearance of collagen a3 (IV) in the basal lamina during the first postnatal week, the receptor tyrosine kinase erbB3 soon after birth, and Nacetylgalactosamine- (GalNAc-) terminated sugars recognized by the lectin VVA-B4 during the second postnatal week
• on the postsynaptic membrane, the density of junctional folds underlying nerve terminals was markedly decreased at mutant synapses; this is first detectable at P5, and the lower density persisted into adulthood
• in mutant mice, a distinct subsynaptic cytoplasmic compartment failed to form: there appeared to be little distance and few organelles intervening between the postsynaptic plasma membrane and the myofibrillar network in mutants
• the geometry of nerve endings was remarkably normal; the primary gutters were directly apposed by nerve terminal branches
|
|
• although all AChR-containing regions of the postsynaptic membrane were covered by nerve terminals, some thin axonal processes extend beyond the endplate region, forming 'terminal sprouts'
|
behavior/neurological
|
• at around 1 month of age mutant mice become noticeably weaker than littermate controls
|
|
• at around 1 month of age mutant mice become less active than littermate controls
|
muscle
|
• at about 5 weeks of age, mutant muscle becomes thin and atrophic
• no obvious deficits are seen other than muscle atrophy; no signs of muscle necrosis or apoptosis were evident by light or electron microscopy
|
