Phenotypes associated with this allele

• Allele Symbol: Stac3^{tm1a(KOMP)Wtsi}
• Allele Name: targeted mutation 1a, Wellcome Trust Sanger Institute
• Allele ID: MGI:4365152
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Stac3^tm1a(KOMP)Wtsi/Stac3^tm1a(KOMP)Wtsi	B6(Cg)-Stac3^tm1a(KOMP)Wtsi	MGI:5544568
hm2	Stac3^tm1a(KOMP)Wtsi/Stac3^tm1a(KOMP)Wtsi	involves: C57BL/6N	MGI:5790243

Genotype
MGI:5544568

hm1

• Allelic Composition: Stac3^{tm1a(KOMP)Wtsi}/Stac3^{tm1a(KOMP)Wtsi}
• Genetic Background: B6(Cg)-Stac3^{tm1a(KOMP)Wtsi}

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

Curved body shape and dropping forelimbs in Stac3^{tm1a(KOMP)Wtsi}/Stac3^{tm1a(KOMP)Wtsi} mutants

mortality/aging

neonatal lethality, complete penetrance ( J:200631 )

• homozygotes die at birth but are born in normal Mendelian ratios

• heart beating when fetus is removed from uterus

behavior/neurological

unresponsive to tactile stimuli ( J:200631 )

• fetuses do not respond to prodding

abnormal posture ( J:200631 )

• curved body

abnormal limb posture ( J:200631 )

• dropping forelimbs

no spontaneous movement ( J:200631 )

• fetuses are never seen to move

muscle

abnormal extensor digitorum longus morphology ( J:200631 )

• 70% of myosin heavy chain positive cells have central nuclei relative to 11% in control mice

• total number of myofibers is 26% or 18% less than that of wild-type or heterozygous controls, respectively

• average cross-sectional area of myofibers is 20% greater than that of wild-type or heterozygous controls

• disproportional number of myofibers with larger cross-sectional areas

• myofibrils are fewer, smaller, disorganized and sometimes fragmented

• however, average size of EDL muscle is relatively normal

abnormal Z line morphology ( J:200631 )

• streaming Z-lines are observed in EDL muscle

abnormal skeletal muscle fiber morphology ( J:200631 )

• most skeletal myofibers have centrally located nuclei and appear round on cross sections

• EDL myofibers have fewer, smaller, disorganized and sometimes fragmented myofibrils

increased skeletal muscle fiber diameter ( J:200631 )

• average cross-sectional area of myofibers in EDL muscle is 20% greater than that of wild-type or heterozygous controls

centrally nucleated skeletal muscle fibers ( J:200631 )

• most skeletal myofibers have centrally located nuclei, as shown by H&E staining of diaphragm, tongue, tibialis anterior, and extensor digitorum longus (EDL) muscles

• 70% of myosin heavy chain positive cells in EDL muscle show centrally located nuclei relative to 11% in control mice

decreased skeletal muscle fiber number ( J:200631 )

• total number of myofibers in neonatal EDL muscle is 26% or 18% less than that of wild-type or heterozygous controls, respectively

thin diaphragm muscle ( J:200631 )

• diaphrams are slightly thinner than normal at birth

growth/size/body

decreased fetal weight ( J:200631 )

• weight at E18.5 is 11% less than heterozygotes and 14% less than wild type

cardiovascular system

cardiovascular system phenotype ( J:200631 )

N • heart beating when fetus is removed from uterus

limbs/digits/tail

abnormal extensor digitorum longus morphology ( J:200631 )

• 70% of myosin heavy chain positive cells have central nuclei relative to 11% in control mice

• total number of myofibers is 26% or 18% less than that of wild-type or heterozygous controls, respectively

• average cross-sectional area of myofibers is 20% greater than that of wild-type or heterozygous controls

• disproportional number of myofibers with larger cross-sectional areas

• myofibrils are fewer, smaller, disorganized and sometimes fragmented

• however, average size of EDL muscle is relatively normal

Genotype
MGI:5790243

hm2

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

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 )

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

• 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

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