Phenotypes Associated with This Genotype

Genotype
MGI:7450790

• Allelic Composition: Stim1^tm1.1Pg/Stim1⁺
• Genetic Background: involves: C57BL/6

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

growth/size/body

enlarged heart ( J:285187 )

• an increase in heart size is seen at 12 months

decreased body size ( J:285187 )

decreased body weight ( J:285187 )

• mice weigh less at all time points evaluated (1, 3, 6, and 12 months)

enlarged spleen ( J:285187 )

• an increase in spleen/body weight ratio is seen at 3 months

behavior/neurological

tremors ( J:285187 )

• with age, mice show tremors

impaired coordination ( J:285187 )

• mice perform worse on the rotarod or the treadmill already at 3 months

decreased grip strength ( J:285187 )

• mice perform similar to wild-type mice in the grip strength and hanging test, although reduced performance is seen around 2-3 months, which then recovers to normal levels

muscle

abnormal skeletal muscle morphology ( J:285187 )

• enlarged mitochondria with abnormal morphology, such as hypertrophic mitochondria with loss of the mitochondrial crest, which sometimes form circular structures are seen in 6-month-old quadriceps and upper biceps; some mitochondria are located in a subplasmallemal position

• no sarcomeric structures are seen in the circular structures formed by mitochondria, although pseudo-aggregate structures are at times seen and resemble characteristics of human disorders, but are disorganized and chaotic; pseudo-aggregates are not seen at 12 months of age

decreased quadriceps weight ( J:285187 )

• by 3 months of age

decreased gastrocnemius weight ( J:285187 )

• by 3 months of age

increased soleus weight ( J:285187 )

• soleus muscle weighs more than in wild-type mice at 6 and 12 months of age

abnormal skeletal muscle fiber morphology ( J:285187 )

• partial disorganization of myofibrils

• the frequency distribution of type IIa myosin fibers is increased in quadriceps, however no differences seen in the extensor digitorium longus

• the frequency distribution of type IIa and type I myosin fibers is decreased in the soleus and a parallel increase in fibers that are negative for both type IIa and type I myosin

decreased skeletal muscle fiber diameter ( J:285187 )

• cross-sectional area of tibialis anterior fibers shows a higher frequency of smaller areas and this worsens with age; similar trend is seen in quadriceps and extensor digitorum longus but not soleus

increased variability of skeletal muscle fiber size ( J:285187 )

centrally nucleated skeletal muscle fibers ( J:285187 )

• muscles show necrosis and regeneration with newly formed myofibers with central nuclei

decreased skeletal muscle weight ( J:285187 )

• the gastrocnemius and quadriceps muscles weigh less than in wild-type mice at 3 months and all muscles evaluated, except for soleus, weigh less at 12 months

skeletal muscle endomysial fibrosis ( J:285187 )

• endomysial inflammatory infiltrates and cytoplasmic fuscinophilic areas are seen in 6-month-old quadriceps and upper biceps

skeletal muscle necrosis ( J:285187 )

abnormal muscle physiology ( J:285187 )

• myotubes show an augmented calcium entry upon store depletion (SOCE) at 1 month and the increased SOCE is retained throughout all time points compared to wild-type myotubes

• slope, peak Ca²⁺ entry and area under the curve are increased compared to wild-type myotubes, except at 1 month, when the slope appears similar

myopathy ( J:285187 )

• muscles show a myopathic process from 1 month and worsens with age and is characterized by marked fiber size variability, necrosis and regeneration with newly formed myofibers with central nuclei, and increased connective tissue

immune system

enlarged spleen ( J:285187 )

• an increase in spleen/body weight ratio is seen at 3 months

decreased NK cell number ( J:285187 )

• the number of NK cells in the spleen is reduced

• however, no differences in the frequency of T cells, B cells, CD11b+ cells, total granulocytes, and regulatory T cells are seen at 6 months of age

increased Ly6C high monocyte number ( J:285187 )

• the number of Ly6C^high monocytes is increased

decreased Ly6C low monocyte number ( J:285187 )

• levels of Ly6C^low monocytes are reduced

homeostasis/metabolism

abnormal circulating creatine kinase level ( J:285187 )

• only a small difference in creatine kinase levels is seen but a significant variability in creatine kinase levels is seen

increased bleeding time ( J:285187 )

• increase in bleeding time is seen in the tail test

hematopoietic system

enlarged spleen ( J:285187 )

• an increase in spleen/body weight ratio is seen at 3 months

thrombocytopenia ( J:285187 )

• thrombocytopenia is seen at all ages

decreased NK cell number ( J:285187 )

• the number of NK cells in the spleen is reduced

• however, no differences in the frequency of T cells, B cells, CD11b+ cells, total granulocytes, and regulatory T cells are seen at 6 months of age

increased Ly6C high monocyte number ( J:285187 )

• the number of Ly6C^high monocytes is increased

decreased Ly6C low monocyte number ( J:285187 )

• levels of Ly6C^low monocytes are reduced

cardiovascular system

enlarged heart ( J:285187 )

• an increase in heart size is seen at 12 months

limbs/digits/tail

decreased quadriceps weight ( J:285187 )

• by 3 months of age

decreased gastrocnemius weight ( J:285187 )

• by 3 months of age

increased soleus weight ( J:285187 )

• soleus muscle weighs more than in wild-type mice at 6 and 12 months of age

skeleton

abnormal spine curvature ( J:285187 )

• mice display an arched back with age that worsens over time

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
tubular aggregate myopathy 1		DOID:0080089	OMIM:160565	J:285187