Phenotypes Associated with This Genotype

Genotype
MGI:2671994

• Allelic Composition: Chrne^tm1Vwi/Chrne^tm1Vwi
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:36557 )

• mutant mice die 2 to 3 months after birth

behavior/neurological

decreased grip strength ( J:36557 )

• at P20, grip strength appears similar between mutant and control mice; strength decreases progressively in mutant mice, unlike control animals where strength increases with age; around P40, grip strength of mutant mice decreased to 10-20% compared to controls

weakness ( J:36557 )

• with age, mutant mice gradually lose the ability to climb or to bend their body upward when suspended by their tail

growth/size/body

decreased body weight ( J:36557 )

• at P28, the body weight of mutant male animals is at least 40% smaller than that of controls

muscle

decreased muscle weight ( J:36557 )

• at P28-P35 the net weight of slow and fast twitch leg muscles of mutant mice is less than half the weight of muscles from controls

abnormal skeletal muscle morphology ( J:36557 )

• at P5, AChR gamma-subunit mRNA levels in muscle are comparable in mutant and control mice; at P34, gamma-subunit mRNA expression is strongly reduced in control animals, but in mutant mice significant amounts of gamma-subunit-specific RNA remains detectable

skeletal muscle atrophy ( J:36557 )

impaired skeletal muscle contractility ( J:36557 )

• the strength of the isometric twitch following direct and indirect stimulation of the skeletal muscle is significantly smaller in the mutant mice than in control mice

nervous system

abnormal neuromuscular synapse morphology ( J:36557 )

• skeletal muscle end plates stain with rhodamine-a-bungarotoxin in adult animals, but the fluorescence intensity is significantly lower in mutant mice than in controls, suggesting a substantial reduction of AChRs in the end plates

abnormal PNS synaptic transmission ( J:36557 )

• in control mice, the developmental switch from skeletal muscle end plate channels with low-to-high conductance is complete by P14-P16, but this switch does not occur in mutant mice and end plate channels remain with low conductance

• impairment of transmission by the mesure of the mean nerve deficit, calculated as the difference in tension time integrals at 100 Hz during muscle or nerve stimulation, is increased in mutant mice, and increases further with higher frequency of stimulation and with the number of stimuli during tetanic stimulation

abnormal miniature endplate potential ( J:36557 )

• at P6, mEPCs from the diaphragm of control and mutant mice were comparable in size and time course; however, the mEPC decay time course in mutant animals at P30 was slower than that of control littermates and are not significantly different from the values measured in early neonatal end plates

• mEPC amplitudes, which in control animals remains almost unchanged between P5 and P30, are reduced by about 40% in mutant muscle; the difference in mEPC amplitudes between control and mutants is pronounced in muscle from P65 to P75 animals

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
congenital myasthenic syndrome 4C		DOID:0110679	OMIM:608931	J:128178