Phenotypes associated with this allele

• Allele Symbol: Dnm2⁺
• Allele Name: wild type
• Allele ID: MGI:2434393
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Dnm2^tm1.1(KOMP)Vlcg/Dnm2^+	C57BL/6N-Dnm2^tm1.1(KOMP)Vlcg/Ucd	MGI:6262304
ht2	Dnm2^tm1.2Pdc/Dnm2^+	involves: 129S1/SvImJ * C57BL/6	MGI:7378855
ht3	Dnm2^tm1.1Ics/Dnm2^+	involves: 129S2/SvPas	MGI:7378856
ht4	Dnm2^tm1.1Ics/Dnm2^+	involves: 129S2/SvPas * C57BL/6	MGI:4848149
ht5	Dnm2^Rbc12/Dnm2^+	involves: C57BL/6	MGI:7378853
ht6	Dnm2^tm2.1Ics/Dnm2^+	involves: C57BL/6J	MGI:6506379
ht7	Dnm2^tm4.1Ics/Dnm2^+	involves: C57BL/6N	MGI:7464907

Genotype
MGI:6262304

ht1

• Allelic Composition: Dnm2^{tm1.1(KOMP)Vlcg}/Dnm2⁺
• Genetic Background: C57BL/6N-Dnm2^{tm1.1(KOMP)Vlcg}/Ucd
• Cell Lines: 16350A-G11

Data Sources

IMPC Data for Dnm2

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

hematopoietic system

decreased mean corpuscular hemoglobin ( J:211773 )

IMPC - UCD

homeostasis/metabolism

increased circulating alkaline phosphatase level ( J:211773 )

♀

IMPC - UCD

nervous system

small superior vagus ganglion ( J:211773 )

♀

IMPC - UCD

reproductive system

enlarged uterus ( J:211773 )

♀

IMPC - UCD

hydrometra ( J:211773 )

♀

IMPC - UCD

Genotype
MGI:7378855

ht2

• Allelic Composition: Dnm2^tm1.2Pdc/Dnm2⁺
• Genetic Background: involves: 129S1/SvImJ * C57BL/6

hematopoietic system

hematopoietic system phenotype ( J:330452 )

N • no red cell abnormalities are detected

Genotype
MGI:7378856

ht3

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

hematopoietic system

anemia ( J:330452 )

• mild anemia that is normocytic

Genotype
MGI:4848149

ht4

• 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

Genotype
MGI:7378853

ht5

• Allelic Composition: Dnm2^Rbc12/Dnm2⁺
• Genetic Background: involves: C57BL/6

hematopoietic system

microcytic anemia ( J:330452 )

• mice exhibit a mild microcytic anemia with reduced mean cellular hemoglobin but normal mean cell hemoglobin concentration and red cell distribution width

• however, red cell number and reticulocyte percentage, and leukocyte and platelet counts are unchanged, spleen size and architecture appear normal, and response to hemolytic anemia induced by treatment with phenylhydrazine (PHZ) is unchanged

abnormal proerythroblast morphology ( J:330452 )

• spleens contain a 2-fold increase in proerythroblasts

• however, erythroid progenitor numbers are unchanged

abnormal erythrocyte morphology ( J:330452 )

• peripheral blood smears are relatively normal, with occasional target cells

decreased hematocrit ( J:330452 )

decreased hemoglobin content ( J:330452 )

• reduction in mean cellular hemoglobin

decreased mean corpuscular hemoglobin ( J:330452 )

• peripheral blood smears are relatively normal, with occasional hypochromic red cells

abnormal bone marrow cell physiology ( J:330452 )

• bone marrow cells from 10-week-old mice show a 50% reduction in transferrin uptake

• however, erythroid cells clear transferrin at a normal rate, suggesting that endosome recycling is unaffected

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:330452 )

N • total iron biding capacity and serum levels of iron, ferritin, and transferrin are normal and all measures of iron stores are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microcytic anemia		DOID:11252	OMIM:206200	J:330452

Genotype
MGI:6506379

ht6

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

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:7464907

ht7

• Allelic Composition: Dnm2^tm4.1Ics/Dnm2⁺
• Genetic Background: involves: C57BL/6N

muscle

abnormal skeletal muscle fiber morphology ( J:329580 )

• rounder at age 8 weeks

decreased skeletal muscle fiber size ( J:329580 )

• hypotrophy at age 8 weeks

mortality/aging

preweaning lethality, incomplete penetrance ( J:329580 )

• many embryos or pups die between E18.5 and P10

• animals that survive past P10 live till at least age 18 months

growth/size/body

decreased body weight ( J:329580 )

• from age P2 to 8 weeks

behavior/neurological

decreased food intake ( J:329580 )

• less milk in stomach at age P2

decreased grip strength ( J:329580 )

• severe decrease in hanging ability from age 3 to 8 weeks

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:329580 )

N • normal blood glucose levels

cellular

abnormal mitochondrial crista morphology ( J:329580 )

• most crista absent in some muscle fiber mitochondria

abnormal mitochondrial shape ( J:329580 )

• some muscle fiber mitochondria rounded

increased mitochondrial size ( J:329580 )

• some muscle fiber mitochondria enlarged