Phenotypes associated with this allele

• Allele Symbol: Thbs1^tm1Hyn
• Allele Name: targeted mutation 1, Richard Hynes
• Allele ID: MGI:2154534
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Thbs1^tm1Hyn/Thbs1^tm1Hyn	either: (involves: 129S2/SvPas * 129/Sv) or (involves: 129S2/SvPas * C57BL/6)	MGI:3032866
hm2	Thbs1^tm1Hyn/Thbs1^tm1Hyn	involves: 129S2/SvPas	MGI:4939902
hm3	Thbs1^tm1Hyn/Thbs1^tm1Hyn	involves: 129S2/SvPas * C57BL/6	MGI:4361456
cx4	Thbs1^tm1Hyn/Thbs1^tm1Hyn Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL/6	MGI:3032769
cx5	Thbs1^tm1Hyn/Thbs1^tm1Hyn Trp53^tm1Tyj/Trp53^+	involves: 129S2/SvPas * C57BL/6	MGI:3032768
cx6	Thbs1^tm1Hyn/Thbs1^tm1Hyn Thbs2^tm1Bst/Thbs2^tm1Bst	involves: 129T2/SvEms * 129X1/SvJ	MGI:3032867
cx7	Apc^Min/Apc^+ Thbs1^tm1Hyn/Thbs1^tm1Hyn	involves: C57BL/6J	MGI:3032868

Genotype
MGI:3032866

hm1

• Allelic Composition: Thbs1^tm1Hyn/Thbs1^tm1Hyn
• Genetic Background: either: (involves: 129S2/SvPas * 129/Sv) or (involves: 129S2/SvPas * C57BL/6)

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

Lordotic curvature of the spine in Thbs1^tm1Hyn/Thbs1^tm1Hyn mice

mortality/aging

prenatal lethality, incomplete penetrance ( J:46182 )

• fewer than expected number of homozygous mutant mice born after heterozygous matings

• incomplete penetrance

cardiovascular system

abnormal lung vasculature morphology ( J:48446 )

• bronchiolar arteries thickened, tortuous, with smooth muscle cell hyperplasia

vascular smooth muscle hyperplasia ( J:48446 )

abnormal heart ventricle morphology ( J:48446 )

abnormal interventricular septum morphology ( J:48446 )

• enlarged myocytes within ventricular septum

pulmonary alveolar hemorrhage ( J:48446 )

• hemorrhage into the alveoli

digestive/alimentary system

esophagogastric junction metaplasia ( J:48446 )

exocrine pancreas hypoplasia ( J:48446 )

stomach epithelial hyperplasia ( J:48446 )

endocrine/exocrine glands

abnormal cystic duct morphology ( J:48446 )

• dilation of ducts adjacent to distended gall bladder

dilated gallbladder ( J:48446 )

• distended gall bladder

abnormal pancreas morphology ( J:48446 )

• increased vascularity

exocrine pancreas hypoplasia ( J:48446 )

pancreatic islet hyperplasia ( J:48446 )

pancreas inflammation ( J:48446 )

hematopoietic system

increased leukocyte cell number ( J:46182 )

increased eosinophil cell number ( J:46182 )

• increased differential percentage

increased neutrophil cell number ( J:46182 )

increased lymphocyte cell number ( J:46182 )

increased monocyte cell number ( J:46182 )

• increased differential percentage

immune system

pancreas inflammation ( J:48446 )

increased leukocyte cell number ( J:46182 )

increased eosinophil cell number ( J:46182 )

• increased differential percentage

increased neutrophil cell number ( J:46182 )

increased lymphocyte cell number ( J:46182 )

increased monocyte cell number ( J:46182 )

• increased differential percentage

lung inflammation ( J:46182 , J:48446 )

• pneumonia arose between 1 and 4 months of life (J:46182)

liver/biliary system

abnormal cystic duct morphology ( J:48446 )

• dilation of ducts adjacent to distended gall bladder

dilated gallbladder ( J:48446 )

• distended gall bladder

muscle

vascular smooth muscle hyperplasia ( J:48446 )

renal/urinary system

abnormal kidney corticomedullary boundary morphology ( J:48446 )

• indistinct cortico-medullary junction

reproductive system

reduced fertility ( J:46182 )

• homozygous matings produced significantly fewer cumulative litters per breeding pair than wild-type matings

decreased litter size ( J:46182 )

respiratory system

pulmonary alveolar hemorrhage ( J:48446 )

• hemorrhage into the alveoli

lung inflammation ( J:46182 , J:48446 )

• pneumonia arose between 1 and 4 months of life (J:46182)

abnormal lung morphology ( J:48446 )

• proximal mucinous metaplasia

abnormal lung vasculature morphology ( J:48446 )

• bronchiolar arteries thickened, tortuous, with smooth muscle cell hyperplasia

increased club cell number ( J:48446 )

bronchial epithelial hyperplasia ( J:48446 )

skeleton

kyphosis ( J:48446 )

lordosis ( J:46182 )

• apparent from birth

integument

abnormal dermal layer morphology ( J:48446 )

• lack of dermal matrix

• increased dermal vascular density

Genotype
MGI:4939902

hm2

• Allelic Composition: Thbs1^tm1Hyn/Thbs1^tm1Hyn
• Genetic Background: involves: 129S2/SvPas

integument

integument phenotype ( J:133700 )

N • normal cutaneous architecture is maintained in myocutaneous skin flap preparations

abnormal skin physiology ( J:133700 )

• improved myocutaneous skin flap survival 7 days after the surgery as compared to controls

• reduced necrosis

limbs/digits/tail

abnormal hindlimb morphology ( J:133700 )

• better tissue survival after proximal ligation of the external iliac and common femoral

• minimal or no clinical evidence of tissue necrosis

• increased vascular remodeling and vascular perfusion by 1 week after the operation

cardiovascular system

abnormal physiological neovascularization ( J:133700 )

• increased vascular remodeling and vascular perfusion by 1 week after proximal ligation of the external iliac and common femoral

cellular

decreased renal tubule apoptosis ( J:104708 )

• at 24-hr of kidney ischemia/reperfusion (IR) injury, mice exhibit a significant reduction in the number of TUNEL-positive tubules in kidney cortices compared with similarly treated wild-type mice

abnormal mitochondrial physiology ( J:133700 )

homeostasis/metabolism

decreased susceptibility to kidney reperfusion injury ( J:104708 )

• at 24-hr of kidney ischemia/reperfusion (IR) injury, mice exhibit significantly lower serum creatinine levels and show significantly less tubular dilatation, cast formation, loss of brush border, focal epithelial vacuolization and necrosis in the cortex than similarly treated wild-type mice

renal/urinary system

decreased renal tubule apoptosis ( J:104708 )

• at 24-hr of kidney ischemia/reperfusion (IR) injury, mice exhibit a significant reduction in the number of TUNEL-positive tubules in kidney cortices compared with similarly treated wild-type mice

decreased susceptibility to kidney reperfusion injury ( J:104708 )

• at 24-hr of kidney ischemia/reperfusion (IR) injury, mice exhibit significantly lower serum creatinine levels and show significantly less tubular dilatation, cast formation, loss of brush border, focal epithelial vacuolization and necrosis in the cortex than similarly treated wild-type mice

Genotype
MGI:4361456

hm3

• Allelic Composition: Thbs1^tm1Hyn/Thbs1^tm1Hyn
• Genetic Background: involves: 129S2/SvPas * C57BL/6

vision/eye

abnormal lacrimal gland physiology ( J:153126 )

• stimulated lacrimal function is abolished compared to in similarly treated wild-type lacrimal gland fragments

• tear peroxidase declines in older mice

• lacrimal function is lost as early as 8 weeks

• lacrimal gland tissue produces more IL17 than in wild-type mice

• apoptosis in the lacrimal gland of young mice is increased compared to in wild-type mice

• mice exhibit deterioration in the lacrimal gland unlike wild-type mice

increased lacrimal gland apoptosis ( J:153126 )

• apoptosis in the lacrimal gland of young mice is increased compared to in wild-type mice

lacrimal gland inflammation ( J:153126 )

• at 24 and 48 weeks, mononuclear infiltrates are increased compared to in wild-type mice

• mice exhibit an increase in CD4+ T cells compared with wild-type mice

abnormal conjunctiva goblet cell number ( J:153126 )

• younger mice exhibit an increase in numbers goblet cells in the conjunctiva while in older mice they are decreased compared to in wild-type mice

decreased conjunctiva goblet cell number ( J:153126 )

• age-related decline in conjunctiva goblet cell density is worse than in wild-type mice

abnormal cornea morphology ( J:153126 )

• older mice exhibit corneal edema unlike wild-type mice

abnormal cornea epithelium morphology ( J:153126 )

• mice exhibit damage in the corneal epithelial barrier unlike wild-type mice

microphthalmia ( J:153126 )

• mice exhibit a progressive reduction in eye size characterized by eye closure and eventual loss of the eye

narrow eye opening ( J:153126 )

• mice develop dry crusty eyes that eventually close

immune system

lacrimal gland inflammation ( J:153126 )

• at 24 and 48 weeks, mononuclear infiltrates are increased compared to in wild-type mice

• mice exhibit an increase in CD4+ T cells compared with wild-type mice

increased CD4-positive, alpha-beta T cell number ( J:153126 )

• in the lacrimal glands

decreased regulatory T cell number ( J:153126 )

• the number of Foxp3+ regulatory T cells in the spleen is decreased compared to in wild-type mice

decreased interferon-gamma secretion ( J:153126 )

• in splenocytes of older mice

increased interleukin-17 secretion ( J:153126 )

• at 8 to 12 weeks, mice exhibit a 2-fold increase in IL17+ splenocytes compared with wild-type mice

• lacrimal gland tissue produces more IL17 than in wild-type mice

• in older mice, IL17 secretion from splenocytes is increased compared to in wild-type mice

increased anti-single stranded DNA antibody level ( J:153126 )

• at 8 weeks, mice exhibit an increase in serum anti-SSA and anti-SSB autoantibodies compared with wild-type mice

hematopoietic system

increased CD4-positive, alpha-beta T cell number ( J:153126 )

• in the lacrimal glands

decreased regulatory T cell number ( J:153126 )

• the number of Foxp3+ regulatory T cells in the spleen is decreased compared to in wild-type mice

endocrine/exocrine glands

abnormal lacrimal gland physiology ( J:153126 )

• stimulated lacrimal function is abolished compared to in similarly treated wild-type lacrimal gland fragments

• tear peroxidase declines in older mice

• lacrimal function is lost as early as 8 weeks

• lacrimal gland tissue produces more IL17 than in wild-type mice

• apoptosis in the lacrimal gland of young mice is increased compared to in wild-type mice

• mice exhibit deterioration in the lacrimal gland unlike wild-type mice

increased lacrimal gland apoptosis ( J:153126 )

• apoptosis in the lacrimal gland of young mice is increased compared to in wild-type mice

lacrimal gland inflammation ( J:153126 )

• at 24 and 48 weeks, mononuclear infiltrates are increased compared to in wild-type mice

• mice exhibit an increase in CD4+ T cells compared with wild-type mice

cardiovascular system

decreased heart rate ( J:148948 )

abnormal systemic arterial blood pressure ( J:148948 )

• DEA/NO treatment causes a greater hypotensive effect than in controls

decreased pulse pressure ( J:148948 )

• significantly decreased relative to controls

increased mean systemic arterial blood pressure ( J:148948 )

• dark cycle mean arterial pressure is significantly increased relative to controls

increased systemic arterial diastolic blood pressure ( J:148948 )

• dark cycle diastolic pressure is increased relative to controls

integument

decreased sensitivity to skin irradiation ( J:139652 )

• hair is preserved after 25 Gy irradiation

• minimal or no skin ulceration 8 weeks after irradiation

• hair follicles and skin architecture are better preserved than in controls

muscle

muscle phenotype ( J:139652 )

N • no leg muscle atrophy after irradiation

N • limb flexibility maintained

abnormal muscle fiber morphology ( J:139652 )

• less loss of muscle fibers and nuclei after irradiation

cellular

cellular phenotype ( J:139652 )

N • mitochondrial viability and function is preserved after irradiation

increased lacrimal gland apoptosis ( J:153126 )

• apoptosis in the lacrimal gland of young mice is increased compared to in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:153126

Genotype
MGI:3032769

cx4

• Allelic Composition: Thbs1^tm1Hyn/Thbs1^tm1Hyn; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:72391 )

• average life span of 149 days

neoplasm

increased pancreas tumor incidence ( J:72391 )

• 2.8% incidence of pancreas adenocarcinoma

increased lymphoma incidence ( J:72391 )

• 53% incidence

increased histiocytic sarcoma incidence ( J:72391 )

• 5.6% incidence

increased carcinoma incidence ( J:72391 )

• 8.3% incidence

increased adenocarcinoma incidence ( J:72391 )

• 5.6% incidence of adenocarcinoma

• 2.8% incidence of pancreas adenocarcinoma

increased small intestine adenocarcinoma incidence ( J:72391 )

• 2.8% incidence

increased sarcoma incidence ( J:72391 )

• 39% incidence of sarcomas, however no osteosarcomas are seen as in single Trp53 mutants

• 5.6% incidence of undifferentiated sarcoma

increased fibrosarcoma incidence ( J:72391 )

• 8.3% incidence

increased hemangiosarcoma incidence ( J:72391 )

• 17% incidence

digestive/alimentary system

increased small intestine adenocarcinoma incidence ( J:72391 )

• 2.8% incidence

endocrine/exocrine glands

increased pancreas tumor incidence ( J:72391 )

• 2.8% incidence of pancreas adenocarcinoma

Genotype
MGI:3032768

cx5

• Allelic Composition: Thbs1^tm1Hyn/Thbs1^tm1Hyn; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

mortality/aging

premature death ( J:72391 )

• average life span of 426 days

neoplasm

increased pancreas tumor incidence ( J:72391 )

• 1.6% incidence of pancreatic adenocarcinomas

• 1.6% incidence of islet cell adenocarcinomas

abnormal tumor morphology ( J:72391 )

• 58% of 19 tumors exhibit loss of heterozygosity for Trp53

increased adenoma incidence ( J:72391 )

• 4.7% incidence

increased lymphoma incidence ( J:72391 )

• 44% incidence

increased histiocytic sarcoma incidence ( J:72391 )

• 17% incidence

increased carcinoma incidence ( J:72391 )

• 33% incidence

increased adenocarcinoma incidence ( J:72391 )

• 1.6% incidence of pancreatic adenocarcinomas

• 1.6% incidence of islet cell adenocarcinomas

• 19% incidence of adenocarcinomas

increased mammary adenocarcinoma incidence ( J:72391 )

• 4.7% incidence

increased liver adenocarcinoma incidence ( J:72391 )

• 1.6% incidence of hepatocarcinoma

increased lung adenocarcinoma incidence ( J:72391 )

• 9.4% incidence

increased squamous cell carcinoma incidence ( J:72391 )

• 14% incidence of ear squamous cell carcinoma

increased sarcoma incidence ( J:72391 )

• 44% incidence of sarcomas

• 1.6% incidence of undifferentiated sarcomas

increased fibrosarcoma incidence ( J:72391 )

• 13% incidence

increased osteosarcoma incidence ( J:72391 )

• 13% incidence

increased papilloma incidence ( J:72391 )

• 1.6% incidence of stomach papilloma

digestive/alimentary system

gastric polyps ( J:72391 )

• 13% incidence of stomach polyps

respiratory system

increased lung adenocarcinoma incidence ( J:72391 )

• 9.4% incidence

integument

increased mammary adenocarcinoma incidence ( J:72391 )

• 4.7% incidence

liver/biliary system

increased liver adenocarcinoma incidence ( J:72391 )

• 1.6% incidence of hepatocarcinoma

skeleton

increased osteosarcoma incidence ( J:72391 )

• 13% incidence

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:72391 )

• 4.7% incidence

increased pancreas tumor incidence ( J:72391 )

• 1.6% incidence of pancreatic adenocarcinomas

• 1.6% incidence of islet cell adenocarcinomas

Genotype
MGI:3032867

cx6

• Allelic Composition: Thbs1^tm1Hyn/Thbs1^tm1Hyn; Thbs2^tm1Bst/Thbs2^tm1Bst
• Genetic Background: involves: 129T2/SvEms * 129X1/SvJ

mortality/aging

prenatal lethality, incomplete penetrance ( J:78876 )

• 1/2 the expected number of double homozygous mutant mice are born

immune system

impaired macrophage chemotaxis ( J:78876 )

• to wound site

lung inflammation ( J:78876 )

• acute and chronic

limbs/digits/tail

abnormal tail morphology ( J:78876 )

• ductile

respiratory system

lung inflammation ( J:78876 )

• acute and chronic

skeleton

lordosis ( J:78876 )

• mild

homeostasis/metabolism

increased bleeding time ( J:78876 )

• prolonged bleeding time

delayed wound healing ( J:78876 )

• prolonger persistence of inflammation and delayed scab loss at site of wound

integument

abnormal skin condition ( J:78876 )

• fragile

cellular

impaired macrophage chemotaxis ( J:78876 )

• to wound site

hematopoietic system

impaired macrophage chemotaxis ( J:78876 )

• to wound site

Genotype
MGI:3032868

cx7

• Allelic Composition: Apc^Min/Apc⁺; Thbs1^tm1Hyn/Thbs1^tm1Hyn
• Genetic Background: involves: C57BL/6J

mortality/aging

premature death ( J:79641 )

neoplasm

increased tumor incidence ( J:79641 )

increased intestinal adenoma incidence ( J:79641 )

increased carcinoma incidence ( J:79641 )

• intestinal carcinoma in situ

digestive/alimentary system

abnormal intestine morphology ( J:79641 )

• intestinal dysplasia

increased intestinal adenoma incidence ( J:79641 )

growth/size/body

weight loss ( J:79641 )

hematopoietic system

anemia ( J:79641 )

skeleton

lordosis ( J:79641 )