Phenotypes associated with this allele

• Allele Symbol: Stim1⁺
• Allele Name: wild type
• Allele ID: MGI:2433790
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Stim1^em1(IMPC)Mbp/Stim1^+	C57BL/6N-Stim1^em1(IMPC)Mbp/MbpMmucd	MGI:6408683
ht2	Stim1^tm1.1Kuro/Stim1^+	C57BL/6-Stim1^tm1.1Kuro	MGI:4821952
ht3	Stim1^Sax/Stim1^+	involves: C3HeB/FeJ * C57BL/6	MGI:3764834
ht4	Stim1^tm1.1Pg/Stim1^+	involves: C57BL/6	MGI:7450790
ht5	Stim1^tm3Ics/Stim1^+	involves: C57BL/6N	MGI:7623214

Genotype
MGI:6408683

ht1

• Allelic Composition: Stim1^em1(IMPC)Mbp/Stim1⁺
• Genetic Background: C57BL/6N-Stim1^em1(IMPC)Mbp/MbpMmucd

Data Sources

IMPC Data for Stim1

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

behavior/neurological

decreased exploration in new environment ( J:211773 )

♀

IMPC - UCD

cardiovascular system

abnormal placenta vasculature ( J:211773 )

IMPC - UCD

enlarged heart ( J:211773 )

♂

IMPC - UCD

embryo

embryonic growth retardation ( J:211773 )

IMPC - UCD

abnormal placenta morphology ( J:211773 )

IMPC - UCD

abnormal placenta vasculature ( J:211773 )

IMPC - UCD

growth/size/body

enlarged heart ( J:211773 )

♂

IMPC - UCD

embryonic growth retardation ( J:211773 )

IMPC - UCD

enlarged kidney ( J:211773 )

♂

IMPC - UCD

enlarged spleen ( J:211773 )

IMPC - UCD

hematopoietic system

increased leukocyte cell number ( J:211773 )

♀

IMPC - UCD

increased neutrophil cell number ( J:211773 )

♀

IMPC - UCD

increased lymphocyte cell number ( J:211773 )

♀

IMPC - UCD

abnormal spleen morphology ( J:211773 )

IMPC - UCD

enlarged spleen ( J:211773 )

IMPC - UCD

immune system

increased leukocyte cell number ( J:211773 )

♀

IMPC - UCD

increased neutrophil cell number ( J:211773 )

♀

IMPC - UCD

increased lymphocyte cell number ( J:211773 )

♀

IMPC - UCD

abnormal spleen morphology ( J:211773 )

IMPC - UCD

enlarged spleen ( J:211773 )

IMPC - UCD

abnormal lymph node morphology ( J:211773 )

♀

IMPC - UCD

enlarged lymph nodes ( J:211773 )

♀

IMPC - UCD

integument

abnormal skin morphology ( J:211773 )

♀

IMPC - UCD

renal/urinary system

abnormal kidney morphology ( J:211773 )

♀

IMPC - UCD

enlarged kidney ( J:211773 )

♂

IMPC - UCD

small kidney ( J:211773 )

♀

IMPC - UCD

vision/eye

abnormal eye morphology ( J:211773 )

♀

IMPC - UCD

cataract ( J:211773 )

IMPC - UCD

microphthalmia ( J:211773 )

IMPC - UCD

abnormal vitreous body morphology ( J:211773 )

IMPC - UCD

Genotype
MGI:4821952

ht2

• Allelic Composition: Stim1^tm1.1Kuro/Stim1⁺
• Genetic Background: C57BL/6-Stim1^tm1.1Kuro

immune system

decreased susceptibility to type I hypersensitivity reaction ( J:130477 )

• passive cutaneous anaphylaxis is reduced

Genotype
MGI:3764834

ht3

• Allelic Composition: Stim1^Sax/Stim1⁺
• Genetic Background: involves: C3HeB/FeJ * C57BL/6

Bone marrow fibrosis, splenomegaly and megakaryocyte hyperplasia in Stim1^Sax/Stim1⁺ mice

hematopoietic system

enlarged spleen ( J:127381 )

• at 6 months of age, spleen to body mass ratio is increased (14.8+/-4.63% compared to 4.1+/-0.23% in wild-type mice)

abnormal thrombopoiesis ( J:127381 )

• despite similar thrombopoeitin (TPO) levels as observed in wild-type mice, injection of TPO did not induce platelet production as it does in wild-type mice

increased megakaryocyte cell number ( J:127381 )

• at 6 months of age, red pulp is expanded and enriched for megakaryocytes (16.6+/-4.3 megakaryocytes per visual field compared to 4.4+/-13 megakaryocytes per visual field in wild-type mice)

thrombocytopenia ( J:127381 )

• platelet counts are lower than in wild-type mice due to decreased platelet lifespan and increased platelet clearance

• however, thrombopoeitin levels and megakaryocyte differentiation are normal

increased spleen red pulp amount ( J:127381 )

• at 6 months of age, red pulp is expanded and enriched for megakaryocytes (16.6+/-4.3 megakaryocytes per visual field compared to 4.4+/-13 megakaryocytes per visual field in wild-type mice)

abnormal platelet activation ( J:127381 )

• mice exhibit preactivation of platelets

• collagen responses and thrombus formation are defective

homeostasis/metabolism

abnormal platelet activation ( J:127381 )

• mice exhibit preactivation of platelets

• collagen responses and thrombus formation are defective

abnormal thrombosis ( J:127381 )

• thrombus formation is delayed (up to 30 minutes compared to 15 minutes in wild-type mice)

• however, 67% of mice form occlusion thrombi within the same time frame as wild-type mice

increased bleeding time ( J:127381 )

• bleed time and total blood loss is increased (59 ul compared to 43 to 75 ul in wild-type mice)

immune system

immune system phenotype ( J:127381 )

N • T cell development and function are normal

N • at 4 weeks and 6 months of age, total cell counts in the spleen and numbers of T and B cell, granulocytes and monocytic cells is normal

enlarged spleen ( J:127381 )

• at 6 months of age, spleen to body mass ratio is increased (14.8+/-4.63% compared to 4.1+/-0.23% in wild-type mice)

abnormal thrombopoiesis ( J:127381 )

• despite similar thrombopoeitin (TPO) levels as observed in wild-type mice, injection of TPO did not induce platelet production as it does in wild-type mice

increased spleen red pulp amount ( J:127381 )

• at 6 months of age, red pulp is expanded and enriched for megakaryocytes (16.6+/-4.3 megakaryocytes per visual field compared to 4.4+/-13 megakaryocytes per visual field in wild-type mice)

skeleton

abnormal bone marrow morphology ( J:127381 )

• at 6 months of age, mice develop bone marrow fibrosis that leads to a reduction in bone marrow cellularity and stromal degeneration

myelofibrosis ( J:127381 )

• at 6 months of age, mice develop bone marrow fibrosis

growth/size/body

enlarged spleen ( J:127381 )

• at 6 months of age, spleen to body mass ratio is increased (14.8+/-4.63% compared to 4.1+/-0.23% in wild-type mice)

Genotype
MGI:7450790

ht4

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

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

Genotype
MGI:7623214

ht5

• Allelic Composition: Stim1^tm3Ics/Stim1⁺
• Genetic Background: involves: C57BL/6N

adipose tissue

decreased subcutaneous adipose tissue amount ( J:277842 )

• reduced fat layer

decreased body fat mass ( J:277842 )

behavior/neurological

behavior/neurological phenotype ( J:277842 )

N • normal behavior in rotarod test

decreased grip strength ( J:277842 )

• reduced grip strength and severely reduced hanging time

decreased locomotor activity ( J:277842 )

• less distance traveled and lower speed in open field test

paresis ( J:277842 )

• upward gaze paresis of the eyes

cellular

abnormal skeletal muscle fiber mitochondrial morphology ( J:277842 )

• swollen mitochondria in TA muscle fibers

decreased mitochondrial number ( J:327797 )

♂ • in soleus and TA muscle

increased skeletal muscle cell apoptosis ( J:327797 )

♂ • increased degeneration-regeneration cycles in soleus and TA muscle fibers

increased endoplasmic reticulum stress ( J:327797 )

♂ • in sarcoplasmic reticulum (SR) of TA muscle

abnormal oxidative phosphorylation ( J:327797 )

♂ • reduced mitochondrial oxygen consumption in soleus and TA muscle

♂ • reduced mitochondrial reactive oxygen species production in soleus muscle

growth/size/body

decreased body fat mass ( J:277842 )

decreased lean body mass ( J:277842 )

decreased body weight ( J:277842 )

• 11.9% reduction in females and 21.3% in males

decreased body length ( J:277842 )

• 7.2% reduction in females and 7.7% in males

increased spleen weight ( J:277842 )

• 55% increase in females and 31% in males

hematopoietic system

increased spleen weight ( J:277842 )

• 55% increase in females and 31% in males

abnormal megakaryocyte morphology ( J:277842 )

• megakaryocyte hyperplasia in spleen

increased neutrophil cell number ( J:277842 )

• in blood and spleen

thrombocytopenia ( J:277842 )

• 78% reduction in females and 79% in males

increased mean platelet volume ( J:277842 )

• 63% increase in females and 74.4% in males

decreased lymphocyte cell number ( J:277842 )

• in blood and spleen

decreased NK T cell number ( J:277842 )

• in spleen

decreased regulatory T cell number ( J:277842 )

• in spleen

increased monocyte cell number ( J:277842 )

• in blood and spleen

homeostasis/metabolism

decreased circulating glucose level ( J:277842 )

increased circulating insulin level ( J:277842 )

decreased circulating calcium level ( J:277842 )

increased circulating phosphate level ( J:277842 )

increased circulating alanine transaminase level ( J:277842 )

increased circulating aspartate transaminase level ( J:277842 )

increased circulating creatine kinase level ( J:277842 )

• 6-8x increase

increased bleeding time ( J:277842 )

improved glucose tolerance ( J:277842 )

♂

decreased alkaline phosphatase activity ( J:277842 )

♀

immune system

increased spleen weight ( J:277842 )

• 55% increase in females and 31% in males

increased neutrophil cell number ( J:277842 )

• in blood and spleen

decreased lymphocyte cell number ( J:277842 )

• in blood and spleen

decreased NK T cell number ( J:277842 )

• in spleen

decreased regulatory T cell number ( J:277842 )

• in spleen

increased monocyte cell number ( J:277842 )

• in blood and spleen

myositis ( J:277842 )

• increased inflammatory cell infiltration

integument

decreased subcutaneous adipose tissue amount ( J:277842 )

• reduced fat layer

thick dermal layer ( J:277842 )

limbs/digits/tail

decreased internal diameter of femur ( J:277842 )

• reduced bone marrow area

decreased internal diameter of tibia ( J:277842 )

• reduced bone marrow area

decreased gastrocnemius weight ( J:277842 )

• 36.6% reduction in females and 19.3% in males

increased soleus weight ( J:277842 )

• 57.3% increase in females and 58.4% in males

mortality/aging

premature death ( J:277842 )

• only 50% of mice live longer than 9 months

lethality throughout fetal growth and development, incomplete penetrance ( J:277842 )

• breeding cages with WT x heterozygotes pairs yield 41% heterozygotes and 59% WT offspring

perinatal lethality, incomplete penetrance ( J:277842 )

• breeding cages with WT x heterozygotes pairs yield 41% heterozygotes and 59% WT offspring

muscle

abnormal muscle weight ( J:277842 )

• increased soleus weight and decreased gastrocnemius weight

• normal TA and EDL weights

abnormal skeletal muscle morphology ( J:277842 )

• increase in internalized nuclei

• no tubular aggregates

decreased gastrocnemius weight ( J:277842 )

• 36.6% reduction in females and 19.3% in males

increased soleus weight ( J:277842 )

• 57.3% increase in females and 58.4% in males

abnormal skeletal muscle fiber morphology ( J:277842 , J:327797 )

• increased proportion of slow-twitch type I fibers (J:277842)

• increased incidence of abnormally shaped (rounded cross-section) fibers (J:277842)

♂ • increased proportion of slow-twitch type I fibers in soleus muscle (J:327797)

abnormal skeletal muscle fiber mitochondrial morphology ( J:277842 )

• swollen mitochondria in TA muscle fibers

centrally nucleated skeletal muscle fibers ( J:277842 )

• increase in internalized nuclei

skeletal muscle fibrosis ( J:277842 )

abnormal muscle physiology ( J:277842 , J:327797 )

• increased Ca2+ resting levels and extracellular Ca2+ influx (J:277842)

• normal Ca2+ storage (J:277842)

♂ • increased Ca2+ resting levels and extracellular Ca2+ influx in soleus and TA muscle (J:327797)

♂ • normal Ca2+ storage (J:327797)

increased skeletal muscle cell apoptosis ( J:327797 )

♂ • increased degeneration-regeneration cycles in soleus and TA muscle fibers

myositis ( J:277842 )

• increased inflammatory cell infiltration

enhanced skeletal muscle regeneration ( J:327797 )

♂ • increased degeneration-regeneration cycles in soleus and TA muscle fibers

impaired muscle relaxation ( J:277842 )

• increased time to relaxation of TA during continuous sciatic nerve stimulation

decreased muscle fatigability ( J:277842 )

• increased time to fatigue of TA during continuous sciatic nerve stimulation

muscle weakness ( J:277842 )

♂ • lower maximal and specific force in the TA after sciatic nerve stimulation

skeleton

abnormal bone structure ( J:277842 )

• reduced cellular density in tibia, femur and lumbar vertebrae

decreased internal diameter of femur ( J:277842 )

• reduced bone marrow area

decreased internal diameter of tibia ( J:277842 )

• reduced bone marrow area

decreased bone trabecula number ( J:277842 )

• in distal femur at age 4 months

decreased bone stiffness ( J:277842 )

• 10% decrease of polar moment of inertia (MOI)

decreased bone strength ( J:277842 )

• 10% decrease of polar moment of inertia (MOI)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Stormorken syndrome		DOID:0060354	OMIM:185070	J:277842 , J:327797
tubular aggregate myopathy 1		DOID:0080089	OMIM:160565	J:277842 , J:327797