Phenotypes Associated with This Genotype

Genotype
MGI:2451017

• Allelic Composition: Mtm1^tm1.1Jman/Y
• Genetic Background: involves: 129T1/Sv * C57BL/6

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

Clinical evaluation of muscle weakness in Mtm1^tm1.1Jman/Y mice

mortality/aging

premature death ( J:81791 , J:179741 )

♂ • occurs at 59 +/- 19 days due to cachexia and respiratory insufficiency (J:81791)

♂ (J:179741)

perinatal lethality, incomplete penetrance ( J:81791 )

♂ • hemizygous males are underrepresented ( 16.6% instead of the expected 25%) suggesting a certain degree of pre- or neonatal lethality, however no time of death was reported

growth/size/body

cachexia ( J:81791 )

♂ • before death

postnatal growth retardation ( J:81791 )

♂ • a progressive growth impairment compared to wild-type littermates reaching a 35% reduction of body weight by 57 days

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:81791 )

♂ • a progressive motor deficit

abnormal physical strength ( J:81791 )

♂ • a decreased muscular strength starting in the hindlimbs at 4-5 weeks

decreased grip strength ( J:179741 )

♂

decreased vertical activity ( J:179741 )

♂

decreased locomotor activity ( J:179741 )

♂

hindlimb paralysis ( J:81791 )

♂ • hindlimbs become completely paralyzed by 8 weeks

muscle

decreased gastrocnemius weight ( J:179741 )

♂

abnormal skeletal muscle fiber morphology ( J:81791 )

♂ • altered emplacement of mitochondria

♂ • myofibrillar disorganization with sarcomeric disarray and Z-ine streaming that may originated from ER dilations

♂ • atrophy and loss of myofibrils

♂ • frequently seen vacuoles do not contain cellular debris as observed in autophagic vacuoles

muscular atrophy ( J:81791 )

♂ • a progressive amyotrophy

skeletal muscle atrophy ( J:179741 )

♂

abnormal muscle physiology ( J:81791 )

♂ • presence of an abnormal central, peripheral, or anarchical pattern of oxidative enzyme activity in myofibers

progressive muscle weakness ( J:81791 , J:179741 )

♂ (J:81791)

♂ (J:179741)

myopathy ( J:81791 )

♂ • skeletal muscle demonstrated a generalized myopathy with fiber size variation, hypotrophy, and progressive accumulation of paracentral or central nuclei

♂ • myogenesis is not delayed

♂ • inflammatory infiltrates and fibrosis, generally present in dystrophic muscle, were absent

♂ • neither necrotic nor apoptotic muscle fibers were seen

skeleton

kyphosis ( J:81791 )

♂ • by 5-7 weeks

respiratory system

respiratory distress ( J:81791 )

♂ • by 8 weeks

limbs/digits/tail

decreased gastrocnemius weight ( J:179741 )

♂

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
centronuclear myopathy		DOID:14717		J:81791