Mouse Genome Informatics
involves: 129S4/SvJae * C57BL/6
phenotype observed in females
phenotype observed in males
N normal phenotype
• at 7-28 weeks of age, male hemizygotes show a ~17% reduction in average body weight relative to wild-type controls

liver/biliary system
• after electrical stimulation of the sympathetic plexus, male hemizygotes show a 78% reduction in the release of glucose from liver relative to wild-type controls
• in contrast, glucose release from liver upon infusion of noradrenaline or glucagon is comparable to that observed in wild-type control livers

• male hemizygotes show a ~10% increase in the maximal amount of glycogen accumulated in liver during the diurnal rhythm relative to wild-type controls
• since the degradation of glycogen is similar, the minimal amount is reached 2 hrs later in mutant liver than in wild-type liver

nervous system
• young male hemizygotes (2-4.5 months of age) show normal mixed afferent and motor nerve conduction in the sciatic nerve and no defects in the refractory periods and motor nerve conduction in the facial nerve relative to age-matched control mice
• no morphologic abnormalities of the myelin sheath are detected in the sciatic nerve at 3 months of age, as determined by electron microscopy
• mice develop a demyelinating peripheral neuropathy after 3 months of age
• onion bulbs, consisting of supernumerary Schwann cells around axons resulting from repeating demyelination and remyelination, develop between 5-12 months of age
• denervated Schwann cells are occasionally observed
• myelinated fibers show an accumulation of adaxonal Schwann cell cytoplasm
• internodes of 9 month old ventral root fibers are shorter and thinner, with abrupt changes in their lengths and myelin thickness along a single fiber
• remyelinated axons contain thin myelin sheaths
• some incisures appear to be abnormally widened
• nerves exhibit separation of the myelin sheath from the axon
• nerves exhibit splitting of the myelin sheath itself
• central nervous system myelin appears normal
• demyelinated and remyelinated axons are seen by 3 months of age in motor and sensory branches of the femoral nerve and in the ventral and dorsal roots and in sciatic nerve
• number of demyelinated and remyelinated axons are increased further between 5-12 months of age in femoral and sciatic nerves
• motor fibers in the femoral and sciatic nerves and ventral roots are more affected than sensory fibers and dorsal roots

• no obvious behavioral abnormalities

Mouse Models of Human Disease
Charcot-Marie-Tooth Disease, X-Linked Dominant, 1; CMTX1 302800 J:36146