Phenotypes Associated with This Genotype

Genotype
MGI:5523468

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

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

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