Phenotypes Associated with This Genotype

Genotype
MGI:5774663

• Allelic Composition: Klhl40^{tm1(KOMP)Vlcg}/Klhl40^{tm1(KOMP)Vlcg}
• Genetic Background: C57BL/6-Klhl40^{tm1(KOMP)Vlcg}
• Cell Lines: 14780A-B6

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

Small size of P8 Klhl40^{tm1(KOMP)Vlcg}/Klhl40^{tm1(KOMP)Vlcg} pups

mortality/aging

postnatal lethality, complete penetrance ( J:213780 )

• 50% of mice die by 7 days of age and none survive past 3 weeks of age

growth/size/body

decreased body size ( J:213780 )

• at P8, surviving mice are visibly smaller than wild-type controls

postnatal growth retardation ( J:213780 )

• mice exhibit reduced growth within several days of birth

muscle

abnormal sarcomere morphology ( J:213780 )

• at P8, a subset of diaphragm muscle fibers show complete loss of sarcomere organization

• however, sarcomere thin filament lengths are not decreased in P5 tibialis anterior muscles

abnormal Z line morphology ( J:213780 )

• at P8, a subset of diaphragm muscle fibers exhibit widened Z-discs that resemble nemaline bodies

• other diaphragm myofibers display irregular, wave-like structures known as Z line streaming

• at P1, diaphragm muscles appear relatively normal; however, subtle Z-line defects may be present

abnormal skeletal muscle morphology ( J:213780 )

• expression analysis of thin filament proteins revealed that nebulin (NEB) is decreased by ~50% while leiomodin 3 (LMOD3) is nearly abolished in P1 and P8 quadriceps muscles, leading to destabilization of thin filaments and sarcomere dysfunction

abnormal muscle physiology ( J:213780 )

• severe skeletal muscle dysfunction that likely contributes to lethality

impaired skeletal muscle contractility ( J:213780 )

• at P1, the maximum tetanic force of whole hind limbs following 150-Hz stimulation is reduced by >50%

muscle weakness ( J:213780 )

• >50% reduction in hind limb strength at P1

myopathy ( J:213780 )

• mice develop a nemaline-like myopathy

cardiovascular system

small heart ( J:213780 )

• at P5-P11, hearts are smaller but otherwise normal

decreased heart rate ( J:213780 )

• at P5, heart rate is decreased by 15%

• however, fractional shortening is relatively normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
nemaline myopathy 8		DOID:0110930	OMIM:615348	J:213780