Phenotypes associated with this allele

• Allele Symbol: Atad3a^{tm1c(KOMP)Wtsi}
• Allele Name: targeted mutation 1c, Wellcome Trust Sanger Institute
• Allele ID: MGI:6197790
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Atad3a^tm1c(KOMP)Wtsi/Atad3a^tm1c(KOMP)Wtsi Myl1^tm1(cre)Sjb/Myl1^+	B6J.Cg-Myl1^tm1(cre)Sjb Atad3a^tm1c(KOMP)Wtsi	MGI:6197947

Genotype
MGI:6197947

cn1

• Allelic Composition: Atad3a^{tm1c(KOMP)Wtsi}/Atad3a^{tm1c(KOMP)Wtsi}; Myl1^tm1(cre)Sjb/Myl1⁺
• Genetic Background: B6J.Cg-Myl1^tm1(cre)Sjb Atad3a^{tm1c(KOMP)Wtsi}

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

cellular

abnormal mitochondrial crista morphology ( J:263681 )

• mostly oriented parallel to outer membrane, sometimes forming concentric circles in tibialis anterior muscle fibers at age 2 and 5 months

• reduced cristae surface per mitochondrion in tibialis anterior muscle fibers at age 2 months

• lamellar structure in tibialis anterior muscle fibers at age 2 months

• loss of lamellar structure with predominant circular structures in tibialis anterior muscle fibers at age 5 months

disorganized mitochondrial cristae ( J:263681 )

• 60% reduction in number of cristae junctions (contact with outer membrane) in tibialis anterior muscle fibers at age 2 months

• mostly oriented parallel to outer membrane, sometimes forming concentric circles in tibialis anterior muscle fibers at ages 2 and 5 months

abnormal muscle fiber mitochondrial morphology ( J:263681 )

• clear matrix areas, electron-dense inclusions, fragmentation and degeneration in tibialis anterior muscle fibers at age 5 months

• drastically reduced mitochondrial mass in focal areas of skeletal muscle fibers

• increased subsarcolemmal mitochondrial proliferation in some muscle fibers

decreased skeletal muscle fiber mitochondrial DNA content ( J:263681 )

• 30% reduction at age 5-6 months, 55% at 12 months and 45% at 18 months in skeletal muscle

• high level of age-related deletions in skeletal muscle at ages 12 months and 18 months

• high level of age-related rearrangements in skeletal muscle at age 20 months

decreased mitochondrial size ( J:263681 )

• in tibialis anterior muscle fibers at age 5 months

abnormal oxidative phosphorylation ( J:263681 )

• 50% reduction in steady-state levels of complex I (Ndufb8) and complex V (Atp5a1) markers in skeletal muscle from age 3 months

• reduction in levels of complex IV marker mt-Co1 in skeletal muscle from age 5 months

• steady-state levels of complex II (Sdha) and complex III (Uqcrc1) markers in skeletal muscle

muscle

abnormal muscle fiber morphology ( J:263681 )

• significantly lower cross-sectional area at age 5 months

• pale cores lacking cytochrome c oxidase and succinate dehydrogenase activity (suggesting lack of mitochondria); small single cores at age 5 months, larger and/or multiple cores at age 18 months

• increased subsarcolemmal cytochrome c oxidase and succinate dehydrogenase activity (suggesting increased number of mitochondria) in some fibers

abnormal muscle fiber mitochondrial morphology ( J:263681 )

• clear matrix areas, electron-dense inclusions, fragmentation and degeneration in tibialis anterior muscle fibers at age 5 months

• drastically reduced mitochondrial mass in focal areas of skeletal muscle fibers

• increased subsarcolemmal mitochondrial proliferation in some muscle fibers

decreased skeletal muscle fiber mitochondrial DNA content ( J:263681 )

• 30% reduction at age 5-6 months, 55% at 12 months and 45% at 18 months in skeletal muscle

• high level of age-related deletions in skeletal muscle at ages 12 months and 18 months

• high level of age-related rearrangements in skeletal muscle at age 20 months

skeletal muscle fiber atrophy ( J:263681 )

♀ • increased empty spaces between fibers at age 18 months

skeletal muscle fiber degeneration ( J:263681 )

• at age 18 months

decreased skeletal muscle weight ( J:263681 , J:263681 )

• reduced quadriceps, gastrocnemius and tibialis anterior muscle weight as percentage of body weight from age 5 months (J:263681)

♀ • gastrocnemius and tibialis anterior at age 18 months (J:263681)

behavior/neurological

abnormal motor coordination/balance ( J:263681 )

♂ • stay on a progressively accelerating cylinder for shorter time in rotarod test

decreased grip strength ( J:263681 )

• reduced maximum grip strength in forelimbs at age 6 months with no further worsening

weakness ( J:263681 )

♂ • activity on treadmill at age 2 months

♂ • increase in falling frequency on treadmill from age 3 months

decreased locomotor activity ( J:263681 )

♂ • decreased travelling distance, ambulatory counts and increased resting time in open field test from age 6 months

homeostasis/metabolism

abnormal cholesterol homeostasis ( J:263681 )

• lipid composition in skeletal muscle at age 2 months

• decreased levels of cholesterol esters (CEs) synthesized in ER and increased levels of CEs obtained from diet in skeletal muscle at age 5 months

• reduced level of total CEs versus free cholesterol in skeletal muscle at age 5 months

skeleton

kyphosis ( J:263681 )

• at age 6 months

growth/size/body

growth/size/body region phenotype ( J:263681 )

N • weight at birth

N • daily food intake at age 5 months

N • heart weight at ages 5 months and 12 months

cachexia ( J:263681 , J:263681 )

♀ • from age 5 months (J:263681)

♂ • from age 2 months (J:263681)