Phenotypes associated with this allele

• Allele Symbol: Obsl1^tm1.1Slan
• Allele Name: targeted mutation 1.1, Stephan Lange
• Allele ID: MGI:6450042
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Obsl1^tm1.1Slan/Obsl1^tm1.1Slan Tg(Myog-cre)1Eno/0	involves: 129 * Black Swiss * C57BL/6 * SJL	MGI:6476965
cn2	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:6476965

cn1

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

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

mortality/aging

mortality/aging ( J:283623 )

N • mice do not exhibit premature death or gross morphological abnormalities

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

increased extensor digitorum longus weight ( J:283623 )

• at 4 months of age, muscle weight to tibia-length ratio is slightly increased for extensor digitorum longus (EDL) muscles

• however, muscle weight to tibia-length ratios for TA, soleus, and gastrocnemius are normal

increased skeletal muscle fiber diameter ( J:283623 )

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

limbs/digits/tail

increased extensor digitorum longus weight ( J:283623 )

• at 4 months of age, muscle weight to tibia-length ratio is slightly increased for extensor digitorum longus (EDL) muscles

• however, muscle weight to tibia-length ratios for TA, soleus, and gastrocnemius are normal

Genotype
MGI:6476968

cn2

• 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