Phenotypes associated with this allele

• Allele Symbol: Dnm2^tm2.1Ics
• Allele Name: targeted mutation 2.1, Mouse Clinical Institute
• Allele ID: MGI:6506378
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Dnm2^tm2.1Ics/Dnm2^+	involves: C57BL/6J	MGI:6506379
cn2	Dnm2^tm1Ueli/Dnm2^tm2.1Ics Tg(Mpz-cre)26Mes/0	involves: C57BL/6J * C57BL/6N * FVB/NTac	MGI:6506449

Genotype
MGI:6506379

ht1

• Allelic Composition: Dnm2^tm2.1Ics/Dnm2⁺
• Genetic Background: involves: C57BL/6J

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

behavior/neurological

behavior/neurological phenotype ( J:288372 )

N • mice show no impaired performance on the hot plate, rotarod, or forepaw grip strength tests at 2 months and 1 year of age, and in the inverted hang motor test at 2 months of age

abnormal gait ( J:288372 )

• minor gait alterations are seen at 2 months and 1 year of age

short stride length ( J:288372 )

decreased locomotor activity ( J:288372 )

• mice travel less distance than controls in the open field at 2 months and 1 year of age

growth/size/body

decreased total tissue mass ( J:288372 )

• mice show a slight reduction in average body mass, with substantial variability at 2 months and 1 year of age

hematopoietic system

increased macrophage cell number ( J:288372 )

• the numbers of macrophages in between myofibers are elevated at 2 months and 1 year of age

• consistent increase in the number of macrophages in tibialis anterior muscle

immune system

immune system phenotype ( J:288372 )

N • mice do not show changes in the abundance of CD4+ T cells, CD8+ T cells, B cells, neutrophils, inflammatory monocytes, macrophages or dendritic cells in the blood and do not develop signs of neutropenia

N • mice challenged with infection by Listeria monocytogenes show no differences in immune cells in blood, spleen, bone marrow or peritoneal cavity compared to controls except for a very small change in B-cell numbers in spleens

increased macrophage cell number ( J:288372 )

• the numbers of macrophages in between myofibers are elevated at 2 months and 1 year of age

• consistent increase in the number of macrophages in tibialis anterior muscle

muscle

abnormal skeletal muscle fiber morphology ( J:288372 )

• an increase in extracellular matrix/fibrotic tissue is seen in soleus muscle at 2 months and 1 year of age, indicating myofiber damage

• marker analysis indicates an increase in fiber regeneration in soleus muscle in 2-month old mice

decreased skeletal muscle fiber diameter ( J:288372 )

• soleus muscle shows a shift toward smaller-caliber fibers at 2 months and 1 year of age

• tibialis anterior muscle shows a shift in fiber diameter frequency distributions toward smaller-caliber fibers

decreased skeletal muscle weight ( J:288372 )

• weight of soleus muscle is decreased in males at 2 months of age and in both males and females at 1 year of age

• tibialis anterior muscle weight is reduced, with some variability at 2 months of age and more uniformity at 1 year of age

abnormal skeletal muscle fiber type ratio ( J:288372 )

• very small, but significant, increase of fiber type II and decrease of fiber type I is seen in soleus muscle at 2 months and 1 year of age

abnormal muscle electrophysiology ( J:288372 )

• the compound muscle action potential amplitude, which includes the muscle response to the motor axon stimulation, is reduced

• a slight, but significant, decrement of the muscle response to repetitive stimulation is seen at 3 and 10 Hz

• however, mice show no changes in compound sensory nerve conduction velocity and amplitude in the PNS compartment and no difference in motor nerve conduction velocity

myopathy ( J:288372 )

• mice develop a mild but definitive and enduring primary myopathy which develops in the absence of neuropathy

• an increase in extracellular matrix/fibrotic tissue is seen in soleus muscle at 2 months and 1 year of age, indicating myofiber damage

• marker analysis indicates an increase in fiber regeneration in soleus muscle in 2-month old mice

nervous system

increased myelin sheath thickness ( J:288372 )

• g-ratio shows slightly lower average values in 1-year old distal tibial nerves, indicating marginally thicker myelin sheaths, especially surrounding small caliber axons

• however, myelin periodicity is not altered and no major signs of demyelination or remyelination are seen in distal tibial nerves indicating that mice do not develop typical features of a dysmyelinating/demyelinating neuropathy up to 1 year of age

abnormal neuromuscular synapse morphology ( J:288372 )

• soleus muscles show a marginal decrease of fully innervated endplates at both 2 months and 1 year of age and a slight increase of partially denervated endplates in 1 year old mice

• however, no significant increase of fully denervated fibers is seen

abnormal action potential ( J:288372 )

• the compound muscle action potential amplitude, which includes the muscle response to the motor axon stimulation, is reduced

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myopathy		DOID:423		J:288372

Genotype
MGI:6506449

cn2

• Allelic Composition: Dnm2^tm1Ueli/Dnm2^tm2.1Ics; Tg(Mpz-cre)26Mes/0
• Genetic Background: involves: C57BL/6J * C57BL/6N * FVB/NTac

nervous system

demyelination ( J:288372 )

• mice show severe demyelinating neuropathy

• nerves show a strong reduction of myelinated axons at P24, with an increase in the number of sorted myelin-competent axons that are not enwrapped by myelin

• cells with engulfed myelin inclusions, indicative of ongoing demyelination, are commonly seen in nerves at P24

• however, the number of sorted axons and numbers of structural myelin aberrations are not changed

• no morphological changes are seen in tibial nerves or sciatic nerves at P5, indicating normal radial axonal sorting and correct onset of myelination

abnormal action potential ( J:288372 )

• electrophysiology shows decreased compound muscle action potential amplitude at P24

decreased nerve conduction velocity ( J:288372 )

• electrophysiology shows reduced motor nerve conduction velocity at P24

• compound sensory nerve conduction velocity and compound sensory amplitude are not detectible in P24 mice