Phenotypes Associated with This Genotype

Genotype
MGI:3527796

• Allelic Composition: Lmna^tm1Gbon/Lmna^tm1Gbon
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

premature death ( J:95528 )

• all mutant males died between 4 and 9 months of age while females died between 7 and 13 months of age

behavior/neurological

impaired coordination ( J:95528 )

• both males and females fell earlier from a rotarod compared to wild-type at 6 months of age

hunched posture ( J:95528 )

• males and females began to show a hunched position and stiff walking posture at 3 months and 6 months of age, respectively

abnormal gait ( J:95528 )

• males and females began to show a stiff walking posture at 3 months and 6 months of age, respectively

bradykinesia ( J:95528 )

• at 6 months of age, spontaneous locomotion tested in an open field was impaired in males but not in females until 8 months of age

cardiovascular system

abnormal myocardial fiber morphology ( J:95528 )

• myocytes of cardiac muscle had very dark, condensed and irregularly distributed heterochromatin, the nuclear membrane sometimes had deep convolutions with the appearance of intranuclear tubules, and had an accumulation of P-Smad2/3 in nuclei

myocardium necrosis ( J:95528 )

• left and right ventricles contained single or small clusters of cardiac muscle cells with degeneration and necrosis

dilated heart atrium ( J:95528 )

enlarged heart ( J:95528 )

dilated heart left ventricle ( J:95528 , J:187399 )

• at 2 months of age, males developed a progressive left ventricle dilation but no left ventricle hypertrophy and this defect occurred later (4 months) and progressed less rapidly in females (J:95528)

• increase in left ventricular end-diastolic diameter and left ventricular end-systolic diameter indicating left ventricular dilation (J:187399)

• treatment with ARRY-371797, a highly selective and potent inhibitor of Mapk14, reduces left ventricular end-diastolic diameter and left ventricular end-systolic diameter (J:187399)

dilated heart right ventricle ( J:95528 )

cardiac fibrosis ( J:95528 )

dilated cardiomyopathy ( J:187399 )

decreased cardiac muscle contractility ( J:187399 )

• decrease in fractional shortening

• treatment with ARRY-371797, a highly selective and potent inhibitor of Mapk14, increases fractional shortening

decreased heart left ventricle muscle contractility ( J:95528 )

• decreased left ventricular shortening indicating a decrease of contractile function

abnormal impulse conducting system conduction ( J:95528 )

• ventricular extra-systoles were observed in 5 month old males during ECG recordings

prolonged PR interval ( J:95528 )

• males at 3 months of age showed a significant increase in the PR interval, indicating atrio-ventricular conduction defects

prolonged QRS complex duration ( J:95528 )

• the QRS complex duration, as a parameter for intraventricular conduction, was significantly increased in 5 month old males

sinoatrial block ( J:95528 )

• frequent sinuatrial blocks are observed in 5 month old males during ECG recordings

growth/size/body

enlarged heart ( J:95528 )

decreased body weight ( J:95528 )

• beginning at 3 months of age, males weighed less than controls while females were slightly lighter but only after 6 months of age

postnatal growth retardation ( J:95528 )

• growth rate of males was reduced after 3 months of age, despite normal feeding behavior

homeostasis/metabolism

decreased circulating glucose level ( J:95528 )

• 6-8 month old males, but not females, had lower levels of serum glucose but no significant differences in the levels of insulin, low density lipoprotein, uric acids, asparate aminotransferase and alanine aminotransferase

increased triglyceride level ( J:95528 )

• 6-8 month old females, but not males, had higher triglycerides levels but no significant differences in the levels of insulin, low density lipoprotein, uric acids, asparate aminotransferase and alanine aminotransferase

muscle

abnormal myocardial fiber morphology ( J:95528 )

• myocytes of cardiac muscle had very dark, condensed and irregularly distributed heterochromatin, the nuclear membrane sometimes had deep convolutions with the appearance of intranuclear tubules, and had an accumulation of P-Smad2/3 in nuclei

myocardium necrosis ( J:95528 )

• left and right ventricles contained single or small clusters of cardiac muscle cells with degeneration and necrosis

dilated cardiomyopathy ( J:187399 )

decreased cardiac muscle contractility ( J:187399 )

• decrease in fractional shortening

• treatment with ARRY-371797, a highly selective and potent inhibitor of Mapk14, increases fractional shortening

decreased heart left ventricle muscle contractility ( J:95528 )

• decreased left ventricular shortening indicating a decrease of contractile function

abnormal hypaxial muscle morphology ( J:95528 )

• moderate quadriceps and triceps abnormalities with myocytes of quadriceps having very dark, condensed and irregularly distributed heterochromatin, the nuclear membrane sometimes had deep convolutions with the appearance of intranuclear tubules, and saw an accumulation of P-Smad2/3 in nuclei

abnormal gastrocnemius morphology ( J:95528 )

• moderate gastrocnemius abnormalities

abnormal soleus morphology ( J:95528 )

• increase of connective tissue in the soleus muscles

• fiber size was variable with increased hypertrophic muscle cells and numerous degenerative fibers

abnormal tibialis anterior morphology ( J:95528 )

• moderate tibialis abnormalities

abnormal diaphragm morphology ( J:95528 )

• increase of connective tissue in the diaphragm

• fiber size was variable with increased hypertrophic muscle cells and numerous degenerative fibers

skeletal muscle fibrosis ( J:95528 )

• increase of connective tissue in the diaphragm and soleus muscles

dystrophic muscle ( J:95528 )

• adult mice develop muscular dystrophy

progressive muscle weakness ( J:95528 )

• diaphragm, soleus, gastrocnemius, quadriceps, triceps, and tibialis anterior muscle weakness

respiratory system

tachypnea ( J:95528 )

• males and females began to exhibit rapid shallow breathing at 3 months and 6 months of age, respectively

limbs/digits/tail

abnormal gastrocnemius morphology ( J:95528 )

• moderate gastrocnemius abnormalities

abnormal soleus morphology ( J:95528 )

• increase of connective tissue in the soleus muscles

• fiber size was variable with increased hypertrophic muscle cells and numerous degenerative fibers

abnormal tibialis anterior morphology ( J:95528 )

• moderate tibialis abnormalities

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dilated cardiomyopathy 1A		DOID:0110425	OMIM:115200	J:187399
Emery-Dreifuss muscular dystrophy		DOID:11726	OMIM:PS310300	J:95528