Phenotypes Associated with This Genotype

Genotype
MGI:4838324

• Allelic Composition: Ttn^tm1.1Isrd/Ttn^tm1.1Isrd
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

cellular

cardiac interstitial fibrosis ( J:165576 )

mortality/aging

prenatal lethality, incomplete penetrance ( J:165576 )

embryonic lethality during organogenesis, incomplete penetrance ( J:165576 )

• based upon significant deviation from Mendelian rations, prenatal loss affects nearly 9/10 of homozygous animals, however at E12 embryo ratios exist at a Mendelain ratio, with the presence of necrotic embryos.

limbs/digits/tail

abnormal limb muscle morphology ( J:165576 )

• Biceps Femoris, gluteus and psoas show the first signs of dystrophy at 6 months of age

abnormal gastrocnemius morphology ( J:165576 )

• signs of dystrophy at 6 months of age

abnormal soleus morphology ( J:165576 )

• signs of dystrophy at 6 months of age

abnormal tibialis anterior morphology ( J:165576 )

• signs of dystrophy at 6 months of age

muscle

dilated cardiomyopathy ( J:165576 )

decreased heart ventricle muscle contractility ( J:165576 )

• LV fractional shortening and ejection fraction are significantly reduced

myositis ( J:165576 )

• ITGAM positive cells in the soleus of 9 month old animals

abnormal M line morphology ( J:165576 )

• modified OBSCN staining, and M band width

abnormal skeletal muscle morphology ( J:165576 )

• pathological features are the presence of fibers with centrally located nuclei and heterogeneity of fiber sizes within the entire muscle area.

abnormal limb muscle morphology ( J:165576 )

• Biceps Femoris, gluteus and psoas show the first signs of dystrophy at 6 months of age

abnormal gastrocnemius morphology ( J:165576 )

• signs of dystrophy at 6 months of age

abnormal soleus morphology ( J:165576 )

• signs of dystrophy at 6 months of age

abnormal tibialis anterior morphology ( J:165576 )

• signs of dystrophy at 6 months of age

increased variability of skeletal muscle fiber size ( J:165576 )

centrally nucleated skeletal muscle fibers ( J:165576 )

skeletal muscle fiber necrosis ( J:165576 )

• soleus has immunohistochemical markers of necrotizing injury in 9 month old animals

dystrophic muscle ( J:165576 )

• soleus is the first muscle to be affected, from 1 month of age and the tibialis anterior, Quadriceps, Psoas, gastrocnemius, gluteus, and Biceps Femoris show the first signs of dystrophy later at 6 months of age

impaired skeletal muscle contractility ( J:165576 )

• In vitro, the specific force generated after tetanic stimulation of the soleus muscle has a a loss of 32 and 40% at 4 and 9 months of age, respectively

immune system

myositis ( J:165576 )

• ITGAM positive cells in the soleus of 9 month old animals

cardiovascular system

dilated heart left ventricle ( J:165576 )

cardiac interstitial fibrosis ( J:165576 )

dilated cardiomyopathy ( J:165576 )

decreased heart ventricle muscle contractility ( J:165576 )

• LV fractional shortening and ejection fraction are significantly reduced

increased left ventricle diastolic pressure ( J:165576 )

increased left ventricle systolic pressure ( J:165576 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive limb-girdle muscular dystrophy type 2J		DOID:0110283	OMIM:608807	J:165576