Phenotypes associated with this allele

• Allele Symbol: Obscn^tm1Chen
• Allele Name: targeted mutation 1, Ju Chen
• Allele ID: MGI:4361272
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Obscn^tm1Chen/Obscn^tm1Chen	involves: 129 * Black Swiss * C57BL/6 * SJL	MGI:6476961
hm2	Obscn^tm1Chen/Obscn^tm1Chen	involves: 129S1/Sv * 129X1/SvJ	MGI:4361274
cn3	Obscn^tm1Chen/Obscn^tm1Chen Obsl1^tm1.1Slan/Obsl1^tm1.1Slan Tg(Myog-cre)1Eno/0	involves: 129 * Black Swiss * C57BL/6 * SJL	MGI:6476968

Genotype
MGI:6476961

hm1

• Allelic Composition: Obscn^tm1Chen/Obscn^tm1Chen
• Genetic Background: involves: 129 * Black Swiss * C57BL/6 * SJL

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

muscle

muscle phenotype ( J:283623 )

N • mice exhibit normal sarcomerogenesis in tibialis anterior (TA) muscles; Z-disc and M-band structures are not significantly altered

N • at 4 months of age, muscle weight to tibia-length ratios for TA, soleus, gastrocnemius and extensor digitorum longus (EDL) muscles are normal

N • no significant changes are noted in the number of centralized nuclei in TA muscle at 4 months of age

abnormal sarcolemma morphology ( J:283623 )

• analysis of subsarcolemmal dystrophin localization in longitudinal sections of TA muscles revealed a patchy and abnormal distribution of dystrophin, indicating increased membrane fragility even at baseline

abnormal sarcoplasmic reticulum morphology ( J:283623 )

• TA muscles show a decrease in protein levels of small ankyrin-1.5 (sAnk1.5, a binding partner for the obscurin-A C terminus) due to increased turnover of the protein

increased skeletal muscle fiber diameter ( J:283623 )

• analysis of cross-sectional areas in TA muscles revealed an increase in fiber size

abnormal muscle physiology ( J:283623 )

• analysis of twitch parameters in EDL muscles revealed increased time-to-peak (TtP) values relative to control and Obsl1 skeletal muscle-knockouts

• however, half-relaxation times remain normal

Genotype
MGI:4361274

hm2

• Allelic Composition: Obscn^tm1Chen/Obscn^tm1Chen
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

muscle

muscle phenotype ( J:153150 )

N • skeletal muscle physiology are normal

abnormal sarcoplasmic reticulum morphology ( J:153150 )

• mice exhibit fewer fully extended longitudinal sarcoplasmic reticulum compared with wild-type mice

centrally nucleated skeletal muscle fibers ( J:153150 )

• in aged mice

myopathy ( J:153150 )

• mild in aged mice

Genotype
MGI:6476968

cn3

• Allelic Composition: Obscn^tm1Chen/Obscn^tm1Chen; Obsl1^tm1.1Slan/Obsl1^tm1.1Slan; Tg(Myog-cre)1Eno/0
• Genetic Background: involves: 129 * Black Swiss * C57BL/6 * SJL

mortality/aging

mortality/aging ( J:283623 )

N • mice are viable and develop normally

muscle

muscle phenotype ( J:283623 )

N • analysis of myofilament structure using sarcomeric alpha-actinin 2 indicated normal sarcomerogenesis in tibialis anterior (TA) muscles

N • immunofluorescence analysis of sarcomeric alpha-actinin 2 and titin-M8 localization revealed that Z-disc and M-band structures are not significantly altered

N • at 4 months of age, muscle weight to tibia-length ratios for TA, soleus, gastrocnemius and extensor digitorum longus (EDL) muscles are normal

N • no significant changes are observed in the number of centralized nuclei in TA muscle at 4 months of age

abnormal sarcolemma morphology ( J:283623 )

• skeletal muscles show a slight decrease in protein levels of utrophin and other dystrophin-sarcoglycan (DSG) components, including alpha-dystrobrevin, whereas levels of tubulin are slightly increased

• although overall dystrophin levels are normal, subsarcolemmal dystrophin localization in longitudinal sections of TA muscles is more patchy and abnormally distributed than in single Obscn^tm1Chen knockouts, indicating exacerbated membrane fragility

• a significant portion of TA muscle fibers are mouse IgG-positive, unlike in single Obscn^tm1Chen knockouts or Obsl1 skeletal muscle-knockouts, suggesting impaired sarcolemmal integrity

• increased membrane fragility leads to upregulation of dysferlin and filamin C proteins (involved in muscle repair), reduced caveolin-1 and TRPC1 protein levels, but normal levels of neuronal nitric oxidase (nNOS) and L-type calcium channel DHPR alpha-2 subunit, indicating potential changes to DSG-associated, but not T-tubule-based ion channels

abnormal sarcoplasmic reticulum morphology ( J:283623 )

• TA muscles show a decrease in small ankyrin-1.5 (sAnk1.5) protein levels similar to that in single Obscn^tm1Chen knockouts

• skeletal muscles show alterations to levels of lumenal SR calcium binding proteins (sarcalumenin and Casq2) as well as sarcoendoplasmic reticulum Ca2+ ATPase (Serca)

• proteome and expression data revealed increases in junctional SR proteins like triadin, junction and ryanodine receptors

decreased skeletal muscle fiber diameter ( J:283623 )

• analysis of cross-sectional areas of TA muscle revealed a decrease in fiber size

abnormal muscle physiology ( J:283623 )

• analysis of twitch parameters in EDL muscles revealed increased time-to-peak (TtP) values relative to control and Obsl1 skeletal muscle-knockouts

• however, half-relaxation times remain normal

homeostasis/metabolism

abnormal enzyme/coenzyme level ( J:283623 )

• monoamine oxidase A and B levels are significantly decreased in TA muscles

increased catalase level ( J:283623 )

• catalase levels are significantly increased in soleus muscle

abnormal glycogen catabolism ( J:283623 )

• muscle glycogen phosphorylase, the rate determining enzyme responsible for glycogen breakdown, is significantly decreased

cellular

abnormal mitochondrial ATP synthesis coupled electron transport ( J:283623 )

• almost all identified mitochondrial electron transport chain proteins are downregulated in soleus and TA muscles

• analysis of whole TA and/or soleus muscle extracts using oxphos antibody cocktail or a Uqcrb antibody revealed slightly or significantly reduced levels of mitochondrial complex I, II, III, IV, and V proteins

reproductive system

reproductive system phenotype ( J:283623 )

N • mice are fertile