Phenotypes Associated with This Genotype

Genotype
MGI:5790243

• Allelic Composition: \Stac3^{tm1a(KOMP)Wtsi}/\Stac3^{tm1a(KOMP)Wtsi}
• Genetic Background: involves: C57BL/6N
• Cell Lines: EPD0101_1_A09

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

Abnormalities of Stac3^{tm1a(KOMP)Wtsi}/Stac3^{tm1a(KOMP)Wtsi} mice

mortality/aging

neonatal lethality, complete penetrance ( J:222015 )

• homozygotes are born in expected Mendelian ratios but die rapidly after birth

• hearts continue beating for several minutes after birth

behavior/neurological

limp posture ( J:222015 )

• neonates show a generally flaccid appearance

paralysis ( J:222015 )

• neonates show complete paralysis

carpoptosis ( J:222015 )

• neonates display wrist drop

growth/size/body

abnormal tongue muscle morphology ( J:222015 )

• reduced muscle mass and aberrant morphology with abnormal clustering of nuclei at E16.5

• myofibers have fewer observable striations, and most have a mottled vacuolated appearance

• sarcomeres are present at E15.5 and E18.5 but appear markedly disorganized at E18.5

abnormal postnatal growth/weight/body size ( J:222015 )

• homozygotes are born with an abnormally rounded lunar shape

respiratory system

primary atelectasis ( J:222015 )

• neonatal alveoli are not inflated and lungs are not buoyant in saline

skeleton

abnormal deltoid tuberosity morphology ( J:222015 )

• the deltoid tuberosity appears severely underdeveloped

abnormal trochanter morphology ( J:222015 )

• the greater trochanter of the femur appears severely underdeveloped

abnormal sternum morphology ( J:222015 )

• sternum abnormalities at E18.5

abnormal costal cartilage morphology ( J:222015 )

• growth defects in costal cartilages at E18.5

abnormal rib morphology ( J:222015 )

• rib abnormalities at E18.5

abnormal spine curvature ( J:222015 )

• abnormal spinal curvature at E18.5

kyphosis ( J:222015 )

• skeletons are abnormally kyphotic at E18.5

abnormal skeleton development ( J:222015 )

• severe reduction in bone ridge formation at major muscle insertion sites, including the deltoid tuberosity of the humerus and the trochanters of the femurs at E18.5

muscle

abnormal sarcomere morphology ( J:222015 )

• electron microscopy of tongues indicates that sarcomeres are present at E15.5 and E18.5 but markedly disorganized at E18.5

abnormal skeletal muscle morphology ( J:222015 )

• appendicular muscles and diaphragm appear smaller and more translucent

abnormal tongue muscle morphology ( J:222015 )

• reduced muscle mass and aberrant morphology with abnormal clustering of nuclei at E16.5

• myofibers have fewer observable striations, and most have a mottled vacuolated appearance

• sarcomeres are present at E15.5 and E18.5 but appear markedly disorganized at E18.5

abnormal skeletal muscle fiber morphology ( J:222015 )

• tongue myofibers are clearly multinucleated but nuclei are typically clustered together instead of being distributed uniformly along the myofiber as in normal muscle

• myofibers appear mottled and vacuolated

• striations are rarely observed in some regions

• myofibrils are formed but show obvious signs of structural heterogeneity and disorganization

centrally nucleated skeletal muscle fibers ( J:222015 )

• myonuclei fail to migrate to the periphery of the fibers by E18.5

abnormal diaphragm morphology ( J:222015 )

• diaphragm appears smaller and more translucent

thin diaphragm muscle ( J:222015 )

decreased skeletal muscle mass ( J:222015 )

• reduced tongue muscle mass at E16.5

impaired skeletal muscle contractility ( J:222015 )

• the deltoid tuberosity and greater trochanter of the femur are severely underdeveloped, suggesting lack of fetal muscle contraction

• in culture, primary myoblasts derived from E18.5 fore- and hindlimbs differentiate and fuse normally, yielding multinucleated myotubes; however, differentiated myotubes never spontaneously twitch, unlike in wild-type controls

• although muscle action potentials are normal, no diaphragm contraction is observed in response to muscle action potentials evoked by electrical stimulation of the phrenic nerve

• electrical field stimulation of E18.5 diaphragms fails to trigger robust tetanic contractions at all tested frequencies, unlike in control diaphragms

• surprisingly, application of 4-CMC (a ryanodine receptor agonist) restores diaphragm muscle contractility, generating a similar magnitude of force as in wild-type controls when normalized for differences in muscle weight

• diaphragms are insensitive to membrane depolarization with potassium chloride (KCl)

abnormal muscle electrophysiology ( J:222015 )

• E18.5 diaphragms are insensitive to membrane depolarization with potassium chloride (KCl)

• in the absence of stimulation, cultured myotubes derived from E18.5 homozygotes fail to exhibit spontaneous twitch-associated Ca²⁺ transients, unlike wild-type and heterozygous myotubes

• cultured myotubes are unresponsive to KCl (as shown by lack of depolarization-induced Ca²⁺ transients) but respond normally to application of 4-CMC, indicating impaired voltage-induced Ca²⁺ release from the sarcoplasmic reticulum

craniofacial

abnormal tongue muscle morphology ( J:222015 )

• reduced muscle mass and aberrant morphology with abnormal clustering of nuclei at E16.5

• myofibers have fewer observable striations, and most have a mottled vacuolated appearance

• sarcomeres are present at E15.5 and E18.5 but appear markedly disorganized at E18.5

homeostasis/metabolism

hypoxia ( J:222015 )

• hypoxia resulting from inability to inspire

abnormal calcium ion homeostasis ( J:222015 )

• complete loss of voltage-induced Ca²⁺ release from the sarcoplasmic reticulum in skeletal muscle

nervous system

abnormal phrenic nerve innervation pattern to diaphragm ( J:222015 )

• increased phrenic nerve branching and defasciculation in the diaphragm at E18.5

abnormal neuromuscular synapse morphology ( J:222015 )

• double-staining of E18.5 diaphragm with Texas red alpha-bungarotoxin to label postsynaptic acetylcholine receptors (AChRs) and an antibody against syntaxin to label presynaptic nerves shows that neuromuscular junctions are properly formed; however, AChR clusters occupy a broader area in the central region of the diaphragm

abnormal miniature endplate potential ( J:222015 )

• E18.5 diaphragms exhibit a significant increase in miniature end-plate potential (mEPP) frequency relative to wild-type controls

• however, mEPP amplitude is normal

limbs/digits/tail

abnormal deltoid tuberosity morphology ( J:222015 )

• the deltoid tuberosity appears severely underdeveloped

abnormal trochanter morphology ( J:222015 )

• the greater trochanter of the femur appears severely underdeveloped

digestive/alimentary system

abnormal tongue muscle morphology ( J:222015 )

• reduced muscle mass and aberrant morphology with abnormal clustering of nuclei at E16.5

• myofibers have fewer observable striations, and most have a mottled vacuolated appearance

• sarcomeres are present at E15.5 and E18.5 but appear markedly disorganized at E18.5