Phenotypes associated with this allele

• Allele Symbol: Rab11a^tm1.1Ngao
• Allele Name: targeted mutation 1.1, Nan Gao
• Allele ID: MGI:5608786
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao Lgr5^tm1(cre/ERT2)Cle/Lgr5^+	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:5608789
cn2	Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao Rab11b^em1Ngao/Rab11b^em1Ngao Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S4/SvJae * C57BL/6 * C57BL/6J * DBA/2	MGI:7766932
cn3	Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5608788
cn4	Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao Tg(Vil1-cre)997Gum/0	involves: 129S4/SvJae * C57BL/6J * SJL	MGI:5608787
cn5	Apc^Min/Apc^+ Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao Tg(Vil1-cre)997Gum/0	involves: 129S4/SvJae * C57BL/6J * SJL/J	MGI:7642164

Genotype
MGI:5608789

cn1

• Allelic Composition: Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao; Lgr5^{tm1(cre/ERT2)Cle}/Lgr5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

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

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:215917 )

• increase in proliferation of intestinal epithelial stem cells and the transit-amplifying cells following tamoxifen induction

Genotype
MGI:7766932

cn2

• Allelic Composition: Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao; Rab11b^em1Ngao/Rab11b^em1Ngao; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BL/6J * DBA/2

mortality/aging

premature death ( J:278932 )

• all mice die by day 3 after tamoxifen administration

Genotype
MGI:5608788

cn3

• Allelic Composition: Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

cellular

abnormal small intestinal crypt cell proliferation ( J:215917 , J:278932 )

• adult mice administered tamoxifen exhibit increased crypt cell proliferation (J:215917)

• 2 days after tamoxifen administration, mice show a mild expansion of Olfm4+ crypt based columnar stem cells indicating entry of enterocytes into mitosis (J:278932)

digestive/alimentary system

abnormal small intestinal crypt cell proliferation ( J:215917 , J:278932 )

• adult mice administered tamoxifen exhibit increased crypt cell proliferation (J:215917)

• 2 days after tamoxifen administration, mice show a mild expansion of Olfm4+ crypt based columnar stem cells indicating entry of enterocytes into mitosis (J:278932)

immune system

increased interleukin-6 secretion ( J:215917 )

• intestinal organoid cultures induced with tamoxifen produce a 2-fold increase in interleukin-6 secretion

Genotype
MGI:5608787

cn4

• Allelic Composition: Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * SJL

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:278932 )

• mice show higher mortality rate 8 weeks after azoxymethane-dextran sulfate sodium (AOM-DSS) treatment

premature death ( J:215917 )

• survivors show a higher mortality with aging

• germ-free mice show reduced mortality

postnatal lethality, incomplete penetrance ( J:215917 )

• about 40% mortality rate at weaning

• males show a higher mortality rate than females

homeostasis/metabolism

increased cytokine level ( J:278932 )

• mice exhibit a higher baseline level of inflammatory cytokines than wild-type mice

increased incidence of tumors by chemical induction ( J:278932 )

• mice show increased susceptibility to AOM-DSS-induced tumorigenesis

• AOM-DSS-treated mice that survive post 8 weeks form 2 to 6 poorly differentiated c-Myc+ and BrdUrd+ tubular adenomas in the ileum that are not seen in wild-type mice; tumors show complex glandular (cribriforming) structures, marked nuclear pleiomorphism, necrosis, increased mitotic activities, and single infiltrating cells in mucosa, best classified as intramucosal carcinoma

neoplasm

increased intestinal adenoma incidence ( J:278932 )

• mice develop tubular adenomas (low-grade epithelial dysplasia) at juvenile ages

• at 1 year, the distal intestines of approximately 30% of mice develop 2 to 3 well-demarcated tubular adenomas and high-grade dysplasia that exhibit complex glandular (cribriforming) structures, marked pleiomorphism, necrosis, and increased mitotic activities

increased incidence of tumors by chemical induction ( J:278932 )

• mice show increased susceptibility to AOM-DSS-induced tumorigenesis

• AOM-DSS-treated mice that survive post 8 weeks form 2 to 6 poorly differentiated c-Myc+ and BrdUrd+ tubular adenomas in the ileum that are not seen in wild-type mice; tumors show complex glandular (cribriforming) structures, marked nuclear pleiomorphism, necrosis, increased mitotic activities, and single infiltrating cells in mucosa, best classified as intramucosal carcinoma

growth/size/body

decreased body size ( J:215917 )

• runting is seen at a young age

digestive/alimentary system

abnormal intestine morphology ( J:215917 )

• dilated intestinal lumen

abnormal intestinal goblet cell morphology ( J:215917 )

• reduction in goblet cells

abnormal intestinal epithelium morphology ( J:215917 )

• epithelial hyperplasia and dysplasia continue to be present at 5 months of age

abnormal crypts of Lieberkuhn morphology ( J:215917 )

• increase in numbers of cycling crypt cells at all postnatal stages indicating crypt hyperplasia

• enlarged crypt

• however, differentiation of enterocytes and intestinal secretory cell lineages is unaffected

decreased colon length ( J:215917 )

• shortened colon

abnormal small intestinal villus morphology ( J:215917 )

• in neonates, the intestinal villi frequently fuse and branch

decreased small intestinal villus size ( J:215917 )

• intestines show blunted villi

increased intestinal adenoma incidence ( J:278932 )

• mice develop tubular adenomas (low-grade epithelial dysplasia) at juvenile ages

• at 1 year, the distal intestines of approximately 30% of mice develop 2 to 3 well-demarcated tubular adenomas and high-grade dysplasia that exhibit complex glandular (cribriforming) structures, marked pleiomorphism, necrosis, and increased mitotic activities

abnormal digestive system physiology ( J:215917 )

• mice show a stronger intestinal epithelial barrier function than wild-type mice

abnormal intestine physiology ( J:215917 , J:278932 )

• intestinal organoid cultures initiate bud outgrowths more rapidly and contain a larger population of proliferative cells than wild-type cultures (J:215917)

• intestinal organoid cultures from germ-free mice show decreased proliferation (J:215917)

• treatment of intestinal organoids with an NF-kappaB pathway inhibitor, BAY11-0782, results in reduction of cell proliferation (J:215917)

• all mice exhibit irregular cribriform proliferation in villi at 150 days (J:278932)

abnormal small intestinal crypt cell physiology ( J:278932 )

• crypt hyperproliferation and low-grade dysplasia is seen throughout the small intestine from birth

abnormal small intestinal crypt cell proliferation ( J:215917 )

• increase in numbers of cycling crypt cells at all postnatal stages

• germ-free mice show an overall reduction of crypt cell proliferation compared to specific pathogen free conditions

intestinal inflammation ( J:215917 )

• macrophage infiltration into the intestinal submucosa

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:215917 )

• increase in numbers of cycling crypt cells at all postnatal stages indicating crypt hyperplasia

• enlarged crypt

• however, differentiation of enterocytes and intestinal secretory cell lineages is unaffected

immune system

intestinal inflammation ( J:215917 )

• macrophage infiltration into the intestinal submucosa

increased cytokine level ( J:278932 )

• mice exhibit a higher baseline level of inflammatory cytokines than wild-type mice

abnormal cytokine secretion ( J:215917 )

• intestinal organoid cultures produce higher levels of cytokines, including interleukin-6, interleukin-1 beta, and CXCL12

• luminal perfusion of TLR9 (endotoxin-free E.coli DNA) or TLR4 (LPS) agonists drastically activates cytokine responses in germ-free mutants compared to wild-type controls, indicating that intestinal epithelial cells show impaired tolerance to microbial TLR agonists

increased interleukin-1 beta secretion ( J:215917 )

• by intestinal organoid cultures

increased interleukin-6 secretion ( J:215917 )

• by intestinal organoid cultures

• intestinal organoid cultures from germ-free mice show reduced IL-6 secretion

• treatment of intestinal organoids with an NF-kappaB pathway inhibitor, BAY11-0782, results in a reduction of IL-6 production

cellular

abnormal intestinal goblet cell morphology ( J:215917 )

• reduction in goblet cells

abnormal small intestinal crypt cell proliferation ( J:215917 )

• increase in numbers of cycling crypt cells at all postnatal stages

• germ-free mice show an overall reduction of crypt cell proliferation compared to specific pathogen free conditions

Genotype
MGI:7642164

cn5

• Allelic Composition: Apc^Min/Apc⁺; Rab11a^tm1.1Ngao/Rab11a^tm1.1Ngao; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * SJL/J

mortality/aging

decreased tumor-free survival time ( J:278932 )

• mice show higher mortality due to increased tumor burden compared to single Apc^Min mice

neoplasm

increased intestinal adenoma incidence ( J:278932 )

• 2-month-old mice develop twice the number of adenomas that are 5 times larger and occupy larger epithelial fields as compared with tumor fields in single Apc^Min mice

• mice show higher mortality due to increased tumor burden compared to single Apc^Min mice

digestive/alimentary system

increased intestinal adenoma incidence ( J:278932 )

• 2-month-old mice develop twice the number of adenomas that are 5 times larger and occupy larger epithelial fields as compared with tumor fields in single Apc^Min mice

• mice show higher mortality due to increased tumor burden compared to single Apc^Min mice