Phenotypes associated with this allele

• Allele Symbol: Tg(DMWD,DMPK*,SIX5)328Ggo
• Allele Name: transgene insertion 328, Genevieve Gourdon
• Allele ID: MGI:5523461
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
tg1	Tg(DMWD,DMPK*,SIX5)328Ggo/Tg(DMWD,DMPK*,SIX5)328Ggo	involves: 129 * C57BL/6 * DBA/2 * FVB/N	MGI:5523476
tg2	Tg(DMWD,DMPK*,SIX5)328Ggo/Tg(DMWD,DMPK*,SIX5)328Ggo	involves: C57BL/6 * DBA/2	MGI:5523468
tg3	Tg(DMWD,DMPK*,SIX5)328Ggo/0	involves: C57BL/6 * DBA/2	MGI:5523467

Genotype
MGI:5523476

tg1

• Allelic Composition: Tg(DMWD,DMPK*,SIX5)328Ggo/Tg(DMWD,DMPK*,SIX5)328Ggo
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * FVB/N

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

growth/size/body

decreased body size ( J:121539 )

• mutants carrying 700 CTG on one allele and 900 or 1,230 CTG on the other are small in size

postnatal growth retardation ( J:121539 )

• mutants carrying 700 CTG on one allele and 900 or 1,230 CTG on the other exhibit severe growth retardation from birth

mortality/aging

premature death ( J:121539 )

• 60% of mutants carrying 700 CTG on one allele and 900 or 1,230 CTG on the other die before 7 months of age

Genotype
MGI:5523468

tg2

• Allelic Composition: Tg(DMWD,DMPK*,SIX5)328Ggo/Tg(DMWD,DMPK*,SIX5)328Ggo
• Genetic Background: involves: C57BL/6 * DBA/2

skeleton

abnormal tooth morphology ( J:73187 )

• 45% of mutants carrying about 300 CTG repeats on both alleles develop abnormal teeth

craniofacial

abnormal tooth morphology ( J:73187 )

• 45% of mutants carrying about 300 CTG repeats on both alleles develop abnormal teeth

digestive/alimentary system

rectal prolapse ( J:73187 )

• 52% of mutants carrying about 300 CTG repeats on both alleles present with an anal proplapse

growth/size/body

abnormal tooth morphology ( J:73187 )

• 45% of mutants carrying about 300 CTG repeats on both alleles develop abnormal teeth

decreased body size ( J:73187 )

• mutants carrying about 300 CTG repeats on both alleles exhibit a small body size

mortality/aging

lethality, incomplete penetrance ( J:73187 )

• fewer than the expected number of mutants carrying about 300 CTG repeats on both alleles are seen

premature death ( J:73187 )

• rate of mortality before the age of 1 year is increased (20% vs. less than 2% is controls) in mutants with about 300 CTG repeats

muscle

increased variability of skeletal muscle fiber size ( J:73187 )

• heterogeneity in the diameter of muscle fibers is seen in mutants carrying about 300 CTG repeats on both alleles

abnormal diaphragm morphology ( J:196337 )

• diaphragm muscle shows dystrophic alterations in mutants carrying more than 1300 CTG repeats, including centrally located nuclei, an increase in interfasicular connective tissue and presence of infiltrating inflammatory cells

• about 58% of diaphragm muscle fiber nuclei contain between 1 and 7 foci of accumulated DMPK RNA with the expanded CUG repeat

abnormal skeletal muscle fiber type ratio ( J:196337 )

• 14.7% increase in the mean percentage of type I muscle fibers in the diaphragm in mutants carrying more than 1300 CTG repeats

impaired muscle relaxation ( J:73187 )

• myotonia is seen in mutants carrying about 300 CTG repeats on both alleles, preferentially in the extensor muscles of the fore legs

• however, pinch-evoked muscle activity is similar to controls

nervous system

abnormal brain morphology ( J:73187 )

• mutants carrying about 300 CTG repeats on both alleles show a change in tau protein isoform production in the brains, with the higher molecular weight tau isoform barely detectable

abnormal neuromuscular synapse morphology ( J:196337 )

• 20% of diaphragm neuromuscular junction endplates are denervated and have no contact with nerve terminals in mutants carrying more than 1300 CTG repeats

• neuromuscular junction endplates of mutants carrying more than 1300 CTG repeats exhibit lengthened shapes, an 11% decrease in mean endplate area, less complex shape, and a 19.9% reduction in the density of acetylcholine receptors on postsynaptic membranes

abnormal phrenic nerve morphology ( J:196337 )

• severe loss (41%) of phrenic nerve unmyelinated axons in mutants carrying more than 1300 CTG repeats

• phrenic nerves of mutants carrying more than 1300 CTG repeats exhibit aberrant Schwann cell proliferation and increased number of macrophages, and reduced myelin sheath thickness

• however, phrenic motor and brainstem respiratory neurons appear normal

homeostasis/metabolism

decreased blood oxygen saturation level ( J:196337 )

• reduction in arterial blood oxygen saturation in mutants carrying more than 1300 CTG repeats

respiratory system

abnormal respiratory function ( J:196337 )

• mutants carrying more than 1300 CTG repeats exhibit impaired respiratory function, showing a decrease in tidal volume and volume per minute when awake, and decreased respiratory rate and tidal volume when anesthetized

decreased pulmonary respiratory rate ( J:196337 )

• mutants carrying more than 1300 CTG repeats exhibit decreased respiratory rate under anesthesia

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
myotonic dystrophy type 1		DOID:11722	OMIM:160900	J:73187 , J:196337

Genotype
MGI:5523467

tg3

• Allelic Composition: Tg(DMWD,DMPK*,SIX5)328Ggo/0
• Genetic Background: involves: C57BL/6 * DBA/2

craniofacial

abnormal tooth morphology ( J:73187 )

• most mutants with about 300 CTG repeats develop abnormal teeth exhibiting crossed teeth

growth/size/body

abnormal tooth morphology ( J:73187 )

• most mutants with about 300 CTG repeats develop abnormal teeth exhibiting crossed teeth

decreased body size ( J:73187 )

• 5% of mutants with about 300 CTG repeats are smaller; these mice are already smaller at 2 days of age, and their weight at weaning is 50-70% that of controls

decreased body weight ( J:73187 )

• weight at weaning is 50-70% that of controls in 5% of mutants with about 300 CTG repeats

muscle

abnormal skeletal muscle fiber morphology ( J:73187 )

• infiltration of fatty tissue into muscle is seen in mutants with about 300 CTG repeats

increased variability of skeletal muscle fiber size ( J:73187 )

• heterogeneity in the diameter of muscle fibers is seen in mutants with about 300 CTG repeats

centrally nucleated skeletal muscle fibers ( J:73187 )

• large numbers of centronucleated muscle fibers in the soleus and sternomastoid muscles are seen in mutants with about 300 CTG repeats

skeletal muscle fibrosis ( J:73187 )

• muscle fibrosis in mutants with about 300 CTG repeats

impaired muscle relaxation ( J:73187 )

• myotonia is seen in mutants with about 300 CTG repeats, preferentially in the extensor muscles of the fore legs

• however, pinch-evoked muscle activity is similar to controls

reproductive system

reproductive system phenotype ( J:73187 )

N • mean litter size is close to normal in mice with about 300 CTG repeats

skeleton

abnormal tooth morphology ( J:73187 )

• most mutants with about 300 CTG repeats develop abnormal teeth exhibiting crossed teeth