Phenotypes associated with this allele

• Allele Symbol: Dsp^tm1Efu
• Allele Name: targeted mutation 1, Elaine Fuchs
• Allele ID: MGI:2156542
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Dsp^tm1Efu/Dsp^tm1Efu Mnx1^tm4(cre)Tmj/Mnx1^+	either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)	MGI:5691408
cn2	Dsp^tm1Efu/Dsp^tm1Efu Tg(KRT14-cre)1Efu/0	involves: 129	MGI:2652092
cn3	Dsp^tm1Efu/Dsp^tm1Efu Myl2^tm1(cre)Krc/Myl2^+	involves: 129 * 129S4/SvJae * C57BL/6	MGI:5660416

Genotype
MGI:5691408

cn1

• Allelic Composition: Dsp^tm1Efu/Dsp^tm1Efu; Mnx1^tm4(cre)Tmj/Mnx1⁺
• Genetic Background: either: (involves: 129S1/Sv * C57BL/6) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

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

nervous system

delayed axon extension ( J:219630 )

• seven days after quadriceps femoris nerve crush, axon outgrowth from lesion site is significantly less than in wild-type

abnormal sciatic nerve morphology ( J:219630 )

• sciatic functional index (SFI), following sciatic nerve crush, is worse in mutant as compared to wild-type

• initial decline is similar, but recovery is slower and does not reach initial state of function after 35 days

• toe spreading is worse after crush as compared to wild-type

impaired ability to fire action potentials ( J:219630 )

• compound muscle action potential (CMAP) is reduced following sciatic nerve crush and does not fully recover

decreased nerve conduction velocity ( J:219630 )

• nerve conduction velocity (NCV) is reduced following sciatic nerve crush as compared to wild-type, but recovers by 35 days

delayed peripheral nervous system regeneration ( J:219630 )

• regeneration of motor fibers is delayed at 14 days and 28 days following quadriceps femoris nerve crush as compared to wild-type

• reduced number of motor fibers at 14 days and 28 days following quadriceps femoris nerve crush as compared to wild-type

cellular

delayed axon extension ( J:219630 )

• seven days after quadriceps femoris nerve crush, axon outgrowth from lesion site is significantly less than in wild-type

Genotype
MGI:2652092

cn2

• Allelic Composition: Dsp^tm1Efu/Dsp^tm1Efu; Tg(KRT14-cre)1Efu/0
• Genetic Background: involves: 129

cellular

abnormal cell adhesion ( J:67797 )

• mice have severe intracellular adhesion defects

integument

abnormal epidermal layer morphology ( J:67797 , J:73084 )

• large sections of the epidermis are missing and visible peeling occurs (J:67797)

• after mechanical stress, newborn mice show epithelial peeling (J:73084)

abnormal epidermis stratum basale morphology ( J:73084 )

• at E18.5, intracellular separation is pronounced

abnormal corneocyte envelope morphology ( J:73084 )

• cornified envelopes are bubble-bath like

abnormal epidermis stratum spinosum morphology ( J:73084 )

• at E18.5, intracellular separation is pronounced

Genotype
MGI:5660416

cn3

• Allelic Composition: Dsp^tm1Efu/Dsp^tm1Efu; Myl2^tm1(cre)Krc/Myl2⁺
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:205990 )

• high doses of epinephrine in combination with exercise can induce sudden cardiac death in mutants that is not seen in controls

premature death ( J:205990 )

• susceptibility to postnatal lethality from 1 month of age onwards, with 50% dying within 2 months of age and 100% mortality by 5 months of age

cardiovascular system

abnormal heart morphology ( J:205990 )

• fatty deposition is seen in the subepicardium, mid-wall region of hearts and in the left ventricle

abnormal myocardium layer morphology ( J:205990 )

• in severely affected regions, hearts show some loss of muscle architecture

abnormal myocardial fiber morphology ( J:205990 )

• rupture of desmosomes and loss of myocyte-myocyte adhesion between neighboring cells as indicated by intercellular gaps in hearts

abnormal intercalated disk morphology ( J:205990 )

• defects in intercalated disc integrity as early as 2.5 weeks of age

increased heart atrium size ( J:205990 )

abnormal subendocardium layer morphology ( J:205990 )

• pronounced pockets of fat deposition are seen within the subepicardium of hearts from 6 week old mice

enlarged heart ( J:205990 )

• 4 week old mice exhibit enlarged hearts

dilated heart ventricle ( J:205990 )

• right and left ventricular chamber dilation in 4 week old mice which is more pronounced in the right ventricle

cardiac fibrosis ( J:205990 )

• extensive fibrosis in the heart, seen in the right and left ventricles and in the septum, but not in the atria

decreased heart ventricle muscle contractility ( J:205990 )

• mice exhibit increased end-diastolic and end-systolic volumes, reduced ejection fraction, and reduced wall thickness in both the right and left ventricle indicating biventricular dilation and depressed systolic function

irregular heartbeat ( J:205990 )

• mice exhibit ventricular arrhythmias that are exacerbated with exercise and catecholamine stimulation

• however, mice exhibit normal heart rate

ventricular premature beat ( J:205990 )

• spontaneous ectopic premature ventricular contractions

abnormal impulse conducting system conduction ( J:205990 )

• epicardial pattern of action potential propagation following ventricular epicardial pacing shows that mutant hearts display pronounced conduction breaks in wavefront propagation within the epicardium

• analysis of action potential propagation in hearts shows prolonged activation time, action potential durations, and action potential dispersion

bundle branch block ( J:205990 )

• hearts exhibit delayed conduction in the right ventricle following atrial pacing, consistent with right bundle branch block

prolonged QRS complex duration ( J:205990 )

• increase in QRS intervals, suggestive of ventricular depolarization delay

ventricular cardiomyopathy ( J:205990 )

• mice exhibit a severe form of ventricular cardiomyopathy similar to a biventricular form of arrhythmogenic right ventricular cardiomyopathy

cellular

increased apoptosis ( J:205990 )

• hearts show an increase in TUNEL+ cells in the cardiac mid-wall and in the subepicardial region of the heart, indicating increased apoptosis

muscle

abnormal myocardium layer morphology ( J:205990 )

• in severely affected regions, hearts show some loss of muscle architecture

abnormal myocardial fiber morphology ( J:205990 )

• rupture of desmosomes and loss of myocyte-myocyte adhesion between neighboring cells as indicated by intercellular gaps in hearts

abnormal intercalated disk morphology ( J:205990 )

• defects in intercalated disc integrity as early as 2.5 weeks of age

decreased heart ventricle muscle contractility ( J:205990 )

• mice exhibit increased end-diastolic and end-systolic volumes, reduced ejection fraction, and reduced wall thickness in both the right and left ventricle indicating biventricular dilation and depressed systolic function

ventricular cardiomyopathy ( J:205990 )

• mice exhibit a severe form of ventricular cardiomyopathy similar to a biventricular form of arrhythmogenic right ventricular cardiomyopathy

abnormal Z line morphology ( J:205990 )

• loss or thickening of Z-lines in severely affected regions of the heart

growth/size/body

enlarged heart ( J:205990 )

• 4 week old mice exhibit enlarged hearts

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
arrhythmogenic right ventricular dysplasia 8		DOID:0110076	OMIM:607450	J:205990