Phenotypes associated with this allele
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dag1tm2Kcam mutation
(2 available);
any
Dag1 mutation
(109 available)
Itgb4tm1Mfel mutation
(0 available);
any
Itgb4 mutation
(107 available)
Tg(Mpz-cre)26Mes mutation
(2 available)
|
|
|
nervous system
|
|
• the inner mesaxon appears disorganized
|
|
|
• abnormally folded myelin with loops, infolding and outfolding is seen in sciatic nerves
• abnormal folding increases with age
|
|
|
• hypomyelination of the ventral roots that is more severe than in single conditional null Dag1tm2Kcam mice
• decrease in myelination becomes evident with age and at 12 months of age includes signs of acute demyelination, myelin degeneration, macrophage infiltration, and remyelination
• macrophages are more numerous in double mutants compared to single conditional null Dag1tm2Kcam mice
|
|
|
• slight but non significant reduction compared to single conditional null Dag1tm2Kcam mice
|
|
|
• slight but non significant increase compared to single conditional null Dag1tm2Kcam mice
|
|
|
• slight but non significant reduction compared to single conditional null Dag1tm2Kcam mice
|
nervous system
|
|
• abnormally folded myelin with loops, infolding and outfolding is seen in sciatic nerves
|
|
|
• hypomyelination of the ventral roots
• decrease in myelination becomes evident with age and at 12 months of age includes signs of acute demyelination, myelin degeneration, macrophage infiltration, and remyelination
|
|
|
• reduced motor action potential amplitude
|
cardiovascular system
|
|
• myocardial cell degeneration marked by eosinophilic myocytes, infiltration of mononuclear cells and significant focal collagen deposition at 10 months of age
• mutants exhibit focal patches of cardiac myocyte membrane damage due to damage expansion of myocardial damage to neighboring myocytes, compared to controls that only show damage in individual myocytes
|
|
|
• some hearts exhibit focal thinning of the left ventricular wall
|
|
|
• increase in cardiac fibrosis, with nearly 9% of the myocardium replaced with focal fibrotic tissue at 10 months of age
|
|
|
• mutants develop progressive dilated cardiomyopathy
• 65% increase in heart weight/body weight ratios
• ratio of the end diastolic volume to mass is increased, indicating dilation of chambers as opposed to increase in overall heart size
• first signs of cardiomyopathy are seen at 7 months of age, with mutants starting to show small focal areas of fibrosis
|
|
|
• reduction in the left ventricular ejection fraction indicating impaired systolic function
|
muscle
|
|
• myocardial cell degeneration marked by eosinophilic myocytes, infiltration of mononuclear cells and significant focal collagen deposition at 10 months of age
• mutants exhibit focal patches of cardiac myocyte membrane damage due to damage expansion of myocardial damage to neighboring myocytes, compared to controls that only show damage in individual myocytes
|
|
|
• mutants develop progressive dilated cardiomyopathy
• 65% increase in heart weight/body weight ratios
• ratio of the end diastolic volume to mass is increased, indicating dilation of chambers as opposed to increase in overall heart size
• first signs of cardiomyopathy are seen at 7 months of age, with mutants starting to show small focal areas of fibrosis
|
|
|
• reduction in the left ventricular ejection fraction indicating impaired systolic function
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dag1tm2Kcam mutation
(2 available);
any
Dag1 mutation
(109 available)
Tg(Myh11-cre)5013Gko mutation
(0 available)
|
|
|
cardiovascular system
|
N |
• mutants do not exhibit alterations in cardiac mass or pathology at 10 months of age
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dag1tm2Kcam mutation
(2 available);
any
Dag1 mutation
(109 available)
Tg(Pax3-cre)1Joe mutation
(0 available)
|
|
|
nervous system
|
|
• in the tibialis muscle, acetylcholine receptors cluster are only found in 3% of neuromuscular junctions (NMJs) unlike in wild-type mice that exhibit clusters in 97% of NMJs
• postsynaptic NMJ maturation is impaired in 97% of muscle fibers compared to in wild-type mice
• however, nerve terminals fully cover postsynaptic sites as in wild-type mice
|
vision/eye
|
|
• pupils are dilated but responsive to light
|
|
|
• synechia of the iris and cornea
|
|
|
• the positive scotopic threshold response is significantly reduced
• the b-wave responses are severely attenuated
|
|
|
• in the Morris water maze and visual cliff test
|
muscle
|
|
• at ~6 weeks, mutant skeletal muscles show loss of dystrophin, dystrobrevin, and the sarcoglycan-sarcospan complex
• during cycles of degeneration, satellite cells are repetitively activated leading to expression of dystroglycan and other components of the DGC in muscle fibers undergoing regeneration
|
|
|
• at ~6 weeks, mutant skeletal muscles, including quadriceps, gastrocnemius, tibialis anterior, biceps, gluteus maximus, and diaphragm, display myonecrosis
|
|
|
• surprisingly, aging mutants develop marked hypertrophy of skeletal muscle fibers
|
|
|
• a >2-fold increase in fiber diameter of the quadriceps and soleus muscle noted at 18 months
|
|
|
• at ~6 weeks, mutant mice show variation of skeletal muscle fiber size
|
|
|
• up to 95% of skeletal muscle fibers exhibit centrally located nuclei
|
|
|
• at 15 months, mutants show a widespread increase in wet muscle weight, esp. in the quadriceps and gastrocnemius muscles, where the weight is doubled
|
|
|
• at ~6 weeks, mutants exhibit hallmarks of muscular dystrophy, such as myonecrosis, central nucleation, and variation of fiber size
• however, despite ongoing cycles of muscle degeneration, aging mutants exhibit only a mild dystrophy with signs of efficient muscle regeneration and marked skeletal muscle hypertrophy but no signs of fibrosis or fat replacement
|
homeostasis/metabolism
growth/size/body
|
|
• at 15 months, mutant mice are significantly larger than control littermates
|
cellular
|
|
• at ~6 weeks, mutant skeletal muscles, including quadriceps, gastrocnemius, tibialis anterior, biceps, gluteus maximus, and diaphragm, display myonecrosis
|
nervous system
|
|
• cerebral, cerebellar and brain stem neuronal migration abnormalities
|
cellular
|
|
• cerebral, cerebellar and brain stem neuronal migration abnormalities
|
growth/size/body
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dag1tm2Kcam mutation
(2 available);
any
Dag1 mutation
(109 available)
Tg(GFAP-cre)25Mes mutation
(2 available)
|
|
|
nervous system
|
|
• cerebral, cerebellar and brain stem neuronal migration abnormalities
|
|
|
• fusion of the cerebral interhemispheric fissure and adjacent cerebellar folia
• malformations resembling polymicrogyria
|
|
|
• granule cells are observed in the subrarachnoid space during postnatal cerebellar development indicating aberrant migration of granule cells
|
|
|
• about 20% increase in brain size
|
|
|
• some mutants show minor dispersion of neuronal cell bodies in the CA1 region
|
|
|
• some mutants show focal irregularities of the dentate granule cell layer in the hippocampus
|
|
|
• cerebral cortical surfaces show widespread discontinuities of the glia limitans (pial surface basal lamina) accompanied by glial neuronal heterotopia within the leptomeninges
|
|
|
• multifocal disarray of neuronal layering in the cerebral cortex
|
|
|
• cerebellar cortical surfaces show widespread discontinuities of the glia limitans (pial surface basal lamina) accompanied by glial neuronal heterotopia within the leptomeninges
|
|
|
• GFAP-immunoreactive astrocytes are prominent in the cerebral cortex, indicating gliosis
|
|
|
• the normally open subarachnoid space is filled with heterotopic astrocytic and neuronal processes
|
|
|
• induction of long-term potentiation (LTP) by high-frequency stimulation is blunted in hippocampal slices, however baseline neurotransmission is unaffected and presynaptic neurotransmitter release is not affected
|
vision/eye
|
|
• significantly reduced positive scotopic threshold response
• significantly increased negative scotopic threshold response
• the b-wave responses are severely attenuated
|
cellular
|
|
• cerebral, cerebellar and brain stem neuronal migration abnormalities
|
growth/size/body
Analysis Tools