Phenotypes associated with this allele

• Allele Symbol: Dnm2^tm1.1Ics
• Allele Name: targeted mutation 1.1, Mouse Clinical Institute
• Allele ID: MGI:4848043
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dnm2^tm1.1Ics/Dnm2^tm1.1Ics	involves: 129S2/SvPas * C57BL/6	MGI:4848148
ht2	Dnm2^tm1.1Ics/Dnm2^+	involves: 129S2/SvPas	MGI:7378856
ht3	Dnm2^tm1.1Ics/Dnm2^+	involves: 129S2/SvPas * C57BL/6	MGI:4848149

Genotype
MGI:4848148

hm1

• Allelic Composition: Dnm2^tm1.1Ics/Dnm2^tm1.1Ics
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

lethality at weaning, incomplete penetrance ( J:166364 )

• all but one mouse dies at weaning

neonatal lethality, incomplete penetrance ( J:166364 )

• nearly all mice die within the first 24 hours after birth

muscle

abnormal skeletal muscle fiber morphology ( J:166364 )

• muscles exhibit intermyofibrillar disorganization compared with wild-type muscles

• muscles exhibit accumulation of mitochondrial and misalignment and proliferation of reticular structures compared to in wild-type muscles

decreased skeletal muscle fiber size ( J:166364 )

• strongly reduced

centrally nucleated skeletal muscle fibers ( J:166364 )

growth/size/body

decreased birth weight ( J:166364 )

postnatal growth retardation ( J:166364 )

• pronounced in surviving mice

cellular

abnormal cell physiology ( J:166364 )

• mouse embryonic fibroblasts exhibit decreased transferring uptake compared with wild-type cells

Genotype
MGI:7378856

ht2

• Allelic Composition: Dnm2^tm1.1Ics/Dnm2⁺
• Genetic Background: involves: 129S2/SvPas

hematopoietic system

anemia ( J:330452 )

• mild anemia that is normocytic

Genotype
MGI:4848149

ht3

• Allelic Composition: Dnm2^tm1.1Ics/Dnm2⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

homeostasis/metabolism

abnormal calcium ion homeostasis ( J:237196 )

• resting cytosolic calcium level is about 50% higher in extensor digitorum longus (EDL) muscle fibers, but not in soleus muscle

• sarcolemmal permeability to calcium is increased and sarcoplasmic reticulum calcium content is higher in EDL

• however, calcium-transient characteristics are unchanged in EDL

muscle

abnormal skeletal muscle fiber morphology ( J:166364 )

• mice exhibit intermyofibrillar disorganization compared with wild-type mice

• beginning at 2 months and increasing in prevalence with age, muscle fibers exhibit centrally localization of mitochondria and sarcoplasmic reticulum within unlike in wild-type muscle

decreased skeletal muscle fiber size ( J:166364 )

• slightly at 2 months and significantly at 8 months in the tibialis anterior and quadriceps

decreased skeletal muscle fiber diameter ( J:166364 )

• at 2 months and increasing in prevalence with age

increased skeletal muscle fiber size ( J:166364 )

• in the soleus between 2 and 8 months

decreased skeletal muscle mass ( J:166364 )

• in the quadriceps at 8 months

• in the gastrocnemius and plantaris at 8 months

• in the tibialis anterior at 2 and 8 months

increased skeletal muscle mass ( J:166364 )

• muscle mass in the soleus and diaphragm is transiently increased compared to in wild-type mice

muscular atrophy ( J:166364 )

• beginning at 2 months and worse at 8 months

abnormal muscle contractility ( J:237196 )

• muscle fiber tetanic force is reduced in EDL

muscle weakness ( J:166364 )

• at 3 weeks of age in the tibialis anterior and soleus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
centronuclear myopathy		DOID:14717		J:237196