Phenotypes Associated with This Genotype

Genotype
MGI:4361456

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

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

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