Phenotypes associated with this allele

• Allele Symbol: St14^tm3Bug
• Allele Name: targeted mutation 3, Thomas H Bugge
• Allele ID: MGI:4361197
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	St14^tm3Bug/St14^tm3Bug	involves: 129S6/SvEvTac	MGI:5634326
cn2	St14^tm2Bug/St14^tm3Bug Tg(CAG-cre/Esr1*)5Amc/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * CBA	MGI:4361221
cn3	St14^tm2Bug/St14^tm3Bug Tg(Vil1-cre)997Gum/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * SJL	MGI:4361214
cn4	St14^tm2Bug/St14^tm3Bug Tg(MMTV-cre)4Mam/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * FVB	MGI:4361220
cn5	St14^tm2Bug/St14^tm3Bug Tg(MMTV-cre)4Mam/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J * FVB/NJ * N:Black Swiss	MGI:5634327

Genotype
MGI:5634326

cn1

• Allelic Composition: St14^tm3Bug/St14^tm3Bug
• Genetic Background: involves: 129S6/SvEvTac

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

digestive/alimentary system

abnormal salivary gland physiology ( J:213072 )

• mice treated with an adenovirus expressing cre-recombinase (Ad-cre) in the submandibular salivary glands exhibit decreased transepithelial electrical potential in the salivary glands, indicating loss of barrier function

• the decrease in transepithelial electrical potential is correlated with decreased salivary flow rate

decreased salivation ( J:213072 )

• mice treated with Ad-cre in the submandibular salivary glands exhibit reduced salivary flow rate following injection of pilocarpine

• salivary gland ductal cells and acinar cells isolated from submandibular salivary glands treated with Ad-cre show an inhibition of volume recovery following hypotonic solution-induced osmotic stress

• however, tear flow rate is not affected

endocrine/exocrine glands

abnormal salivary gland physiology ( J:213072 )

• mice treated with an adenovirus expressing cre-recombinase (Ad-cre) in the submandibular salivary glands exhibit decreased transepithelial electrical potential in the salivary glands, indicating loss of barrier function

• the decrease in transepithelial electrical potential is correlated with decreased salivary flow rate

decreased salivation ( J:213072 )

• mice treated with Ad-cre in the submandibular salivary glands exhibit reduced salivary flow rate following injection of pilocarpine

• salivary gland ductal cells and acinar cells isolated from submandibular salivary glands treated with Ad-cre show an inhibition of volume recovery following hypotonic solution-induced osmotic stress

• however, tear flow rate is not affected

homeostasis/metabolism

decreased salivation ( J:213072 )

• mice treated with Ad-cre in the submandibular salivary glands exhibit reduced salivary flow rate following injection of pilocarpine

• salivary gland ductal cells and acinar cells isolated from submandibular salivary glands treated with Ad-cre show an inhibition of volume recovery following hypotonic solution-induced osmotic stress

• however, tear flow rate is not affected

immune system

immune system phenotype ( J:213072 )

N • mice treated with Ad-cre in the submandibular salivary glands do not exhibit changes in lymphocytic infiltration into the submandibular gland or lacrimal gland, alterations of CD4, CD8 or CD62L expression and Treg numbers, or cytokine or chemokine production in the submandibular salivary glands

Genotype
MGI:4361221

cn2

• Allelic Composition: St14^tm2Bug/St14^tm3Bug; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * CBA

mortality/aging

premature death ( J:153070 )

• mice are moribund within 9 to 10 days of tamoxifen treatment unlike similarly treated control mice

digestive/alimentary system

abnormal enterocyte morphology ( J:153070 )

• tamoxifen-treated mice exhibit disruption of tight junctions unlike similarly treated wild-type mice

abnormal large intestine morphology ( J:153070 )

• tamoxifen-treated mice exhibit dissolution of tissue architecture and pronounced edema of crypts and submucosa in the large intestine unlike in similarly treated control mice

abnormal large intestine crypts of Lieberkuhn morphology ( J:153070 )

• tamoxifen-treated mice exhibit edema of the large intestine crypts unlike in similarly treated control mice

intestinal edema ( J:153070 )

• tamoxifen-treated mice exhibit edema of the large intestine crypts and submucosa unlike in similarly treated control mice

absent digestive secretion ( J:153070 )

• in tamoxifen-treated mice

abnormal enterocyte physiology ( J:153070 )

• tamoxifen-treated mice exhibit a loss of intestinal barrier and increased intestinal permeability unlike similarly treated control mice

• tamoxifen-treated mice exhibit a 1.5-fold increase in epithelial cell transit through colonic crypts compared with similarly treated control mice

• tamoxifen-treated mice exhibit an increase in intestinal cell turnover compared with similarly treated control mice

craniofacial

abnormal facial morphology ( J:153070 )

• tamoxifen-treated mice exhibit scaling and inflammation of the orofacial surfaces unlike similarly treated control mice

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:153070 )

• tamoxifen-treated mice exhibit edema of the large intestine crypts unlike in similarly treated control mice

growth/size/body

abnormal facial morphology ( J:153070 )

• tamoxifen-treated mice exhibit scaling and inflammation of the orofacial surfaces unlike similarly treated control mice

weight loss ( J:153070 )

• in tamoxifen-treated mice despite normal food ingestion

cachexia ( J:153070 )

• in tamoxifen-treated mice

homeostasis/metabolism

intestinal edema ( J:153070 )

• tamoxifen-treated mice exhibit edema of the large intestine crypts and submucosa unlike in similarly treated control mice

integument

alopecia ( J:153070 )

• in tamoxifen-treated mice

abnormal hair follicle morphology ( J:153070 )

• tamoxifen-treated mice exhibit follicular hyperplasia compared with similarly treated control mice

hyperkeratosis ( J:153070 )

• in tamoxifen-treated mice

scaly skin ( J:153070 )

• tamoxifen-treated mice exhibit retention and hyperproliferative ichthyosis unlike similarly treated control mice

skin fibrosis ( J:153070 )

• tamoxifen-treated mice exhibit dermal fibrosis unlike similarly treated control mice

Genotype
MGI:4361214

cn3

• Allelic Composition: St14^tm2Bug/St14^tm3Bug; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * SJL

mortality/aging

premature death ( J:153070 )

• short lifespan of a few weeks to up to a 2 months

digestive/alimentary system

digestive/alimentary phenotype ( J:153070 )

N • mice exhibit normal small intestine morphology

abnormal enterocyte proliferation ( J:153070 )

• mice exhibit hyperproliferation of colonic epithelial cells compared with wild-type mice

abnormal colon morphology ( J:153070 )

• mice exhibit disruption of the colonic tissue architecture, edema, and pervasive inflammation unlike wild-type mice

megacolon ( J:153070 )

• without obstruction

intestinal edema ( J:153070 )

• in the colon

chronic diarrhea ( J:153070 )

• persistent prior to weaning

absent digestive secretion ( J:153070 )

colitis ( J:153070 )

homeostasis/metabolism

intestinal edema ( J:153070 )

• in the colon

growth/size/body

decreased body size ( J:153070 )

immune system

colitis ( J:153070 )

cellular

abnormal enterocyte proliferation ( J:153070 )

• mice exhibit hyperproliferation of colonic epithelial cells compared with wild-type mice

Genotype
MGI:4361220

cn4

• Allelic Composition: St14^tm2Bug/St14^tm3Bug; Tg(MMTV-cre)4Mam/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * FVB

digestive/alimentary system

digestive/alimentary phenotype ( J:153070 )

N • mice exhibit normal salivary gland morphology

decreased salivation ( J:153070 )

• decreased pilocarpine-induced salivation compared with similarly treated wild-type mice

endocrine/exocrine glands

decreased salivation ( J:153070 )

• decreased pilocarpine-induced salivation compared with similarly treated wild-type mice

homeostasis/metabolism

decreased salivation ( J:153070 )

• decreased pilocarpine-induced salivation compared with similarly treated wild-type mice

Genotype
MGI:5634327

cn5

• Allelic Composition: St14^tm2Bug/St14^tm3Bug; Tg(MMTV-cre)4Mam/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6J * FVB/NJ * N:Black Swiss

digestive/alimentary system

submandibular gland inflammation ( J:213072 )

• increase in lymphocytic infiltration area in the submandibular gland

decreased salivation ( J:213072 )

• the salivary flow rate of 24-54 week old mutants is reduced following injection of pilocarpine

endocrine/exocrine glands

submandibular gland inflammation ( J:213072 )

• increase in lymphocytic infiltration area in the submandibular gland

decreased salivation ( J:213072 )

• the salivary flow rate of 24-54 week old mutants is reduced following injection of pilocarpine

lacrimal gland inflammation ( J:213072 )

• increase in lymphocytic infiltration area in the lacrimal gland

hematopoietic system

increased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:213072 )

• the percentage of CD25+Foxp3+ cells within the CD4+ T cell population is increased in the salivary gland draining lymph nodes

increased effector memory CD4-positive, alpha-beta T cell number ( J:213072 )

• loss of CD62L (L-selectin) expression on CD4+ and CD8+ T cells from salivary gland draining lymph node and splenocytes, indicating that the majority of T cells transit to effector T cells

decreased CD4-positive, alpha-beta T cell number ( J:213072 )

• decrease in the number and percentage of CD4+ cells among salivary gland draining lymph node cells and splenocytes

increased effector memory CD8-positive, alpha-beta T cell number ( J:213072 )

• loss of CD62L (L-selectin) expression on CD4+ and CD8+ T cells from salivary gland draining lymph node and splenocytes, indicating that the majority of T cells transit to effector T cells

decreased CD8-positive, alpha-beta T cell number ( J:213072 )

• decrease in the number and percentage of CD8+ cells among salivary gland draining lymph node cells and splenocytes

decreased regulatory T cell number ( J:213072 )

• total number of Treg cells in the salivary gland draining lymph node is decreased

decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:213072 )

• decrease in the CD4+CD25+Foxp3+ Treg cell population in spleens

homeostasis/metabolism

decreased salivation ( J:213072 )

• the salivary flow rate of 24-54 week old mutants is reduced following injection of pilocarpine

immune system

submandibular gland inflammation ( J:213072 )

• increase in lymphocytic infiltration area in the submandibular gland

lacrimal gland inflammation ( J:213072 )

• increase in lymphocytic infiltration area in the lacrimal gland

increased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:213072 )

• the percentage of CD25+Foxp3+ cells within the CD4+ T cell population is increased in the salivary gland draining lymph nodes

increased effector memory CD4-positive, alpha-beta T cell number ( J:213072 )

• loss of CD62L (L-selectin) expression on CD4+ and CD8+ T cells from salivary gland draining lymph node and splenocytes, indicating that the majority of T cells transit to effector T cells

decreased CD4-positive, alpha-beta T cell number ( J:213072 )

• decrease in the number and percentage of CD4+ cells among salivary gland draining lymph node cells and splenocytes

increased effector memory CD8-positive, alpha-beta T cell number ( J:213072 )

• loss of CD62L (L-selectin) expression on CD4+ and CD8+ T cells from salivary gland draining lymph node and splenocytes, indicating that the majority of T cells transit to effector T cells

decreased CD8-positive, alpha-beta T cell number ( J:213072 )

• decrease in the number and percentage of CD8+ cells among salivary gland draining lymph node cells and splenocytes

decreased regulatory T cell number ( J:213072 )

• total number of Treg cells in the salivary gland draining lymph node is decreased

decreased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:213072 )

• decrease in the CD4+CD25+Foxp3+ Treg cell population in spleens

abnormal cytokine secretion ( J:213072 )

• cytokine production is increased in local and systemic immune system

• mice exhibit an increase in IL-1beta, IL-4, IL-5, IL-, IL-10, IL-12-40, IL-13, IL-17, and IFN-gamma cytokines released from cells isolated from salivary gland salivary gland draining lymph node

• cultured splenocytes exhibit an increase in proinflammatory T/B cytokines and a decrease in the Th2 polarizing cytokine IL-4

• increase in proinflammatory cytokines is seen in the serum

abnormal chemokine secretion ( J:213072 )

• cultured splenocytes exhibit an increase in production of MCP-1, MCP-5, MIP-1beta, RANTES and MMP-9 chemokines

• increase in proinflammatory chemokines is seen in the serum

increased autoantibody level ( J:213072 )

• increase in serum levels of anti-SSA/Ro (multiple antigenic peptide (MAP)-Ro273), anti-SSB/La and anti-nuclear antibodies

increased anti-nuclear antigen antibody level ( J:213072 )

vision/eye

lacrimal gland inflammation ( J:213072 )

• increase in lymphocytic infiltration area in the lacrimal gland

decreased tear production ( J:213072 )

• tear flow rate of 24-54 week old mutants is reduced following injection of pilocarpine

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:213072