Phenotypes associated with this allele

• Allele Symbol: Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}
• Allele Name: targeted mutation 9, Hongkui Zeng
• Allele ID: MGI:3809523
• Summary: 15 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+	involves: 129S6/SvEvTac * C57BL/6NCr	MGI:4436851
cn2	Acvr1^tm1Mak/Acvr1^+ Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Olig2^tm1.1(cre)Wdr/Olig2^+	involves: 129 * C57BL/6	MGI:6414954
cn3	Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Rn7sk^tm1.1Mfrye/Rn7sk^tm1.1Mfrye Tg(KRT14-cre/ERT)20Efu/0	involves: 129 * C57BL/6NCrl * CBA * CD-1 * SJL	MGI:7386922
cn4	Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Kras^tm4Tyj/Kras^+ Tg(Pdx1-cre)6Tuv/0 Trp53^tm2Tyj/Trp53^+	involves: 129 * C57BL/6NCrl * FVB/N	MGI:6296002
cn5	Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Kras^tm4Tyj/Kras^+ Prdm1^tm1Clme/Prdm1^tm1Clme Tg(Pdx1-cre)6Tuv/0 Trp53^tm2Tyj/Trp53^+	involves: 129 * C57BL/6NCrl * FVB/N	MGI:6296000
cn6	Chat^tm2(cre)Lowl/Chat^+ Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Sema6a^Gt(KST069)Byg/Sema6a^Gt(KST069)Byg	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6NCr	MGI:5562538
cn7	Atf5^tm1(KOMP)Vlcg/Atf5^tm1(KOMP)Vlcg Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Or4e5^tm1(cre)Rax/Or4e5^+	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6NCr * C57BL/6NTac	MGI:5559544
cn8	Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Syngap1^tm1.1Geno/Syngap1^+	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6 * C57BL/6NCr	MGI:5469877
cn9	Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Hmga2^tm1.1Mmw/Hmga2^+ Kras^tm4Tyj/Kras^+ Tg(Pdx1-cre)6Tuv/0 Trp53^tm2Tyj/Trp53^+	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6NCrl * FVB/N	MGI:6295996
cn10	Rem2^tm1c(EUCOMM)Hmgu/Rem2^tm1c(EUCOMM)Hmgu Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6N * C57BL/6NCrl	MGI:6192637
cn11	Fgf10^tm1.1(cre/ERT2)Sbel/Fgf10^tm1Sms Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6	MGI:5438775
cn12	Hmgcs2^tm1.1Yil/Hmgcs2^tm1.1Yil Lgr5^tm3(cre/ERT2)Cle/Lgr5^+ Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+	involves: 129S6/SvEvTac * C3H * C57BL/6J * C57BL/6NCrl	MGI:8159410
cn13	Gt(ROSA)26Sor^tm1(HBEGF)Awai/Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze Oxt^tm1.1(cre)Dolsn/Oxt^+	involves: 129S6/SvEvTac * C57BL/6	MGI:5523454
cn14	Lgr5^tm3(cre/ERT2)Cle/Lgr5^+ Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl	MGI:8159416
cn15	Mllt11^tm1c(KOMP)Mbp/Mllt11^tm1c(KOMP)Mbp Gt(ROSA)26Sor^tm9(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Cux2^tm1.1(cre)Mull/Cux2^+	involves: C57BL/6 * C57BL/6J * C57BL/6N	MGI:7448866

Genotype
MGI:4436851

ht1

• Allelic Composition: Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6NCr

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

normal phenotype

no abnormal phenotype detected ( J:155793 )

• mice are viable and fertile; used for cre reporter expression analysis

Genotype
MGI:6414954

cn2

• Allelic Composition: Acvr1^tm1Mak/Acvr1⁺; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Olig2^{tm1.1(cre)Wdr}/Olig2⁺
• Genetic Background: involves: 129 * C57BL/6

nervous system

increased oligodendrocyte number ( J:285841 )

• 2-fold increase in the number of oligodendroglial cells in the ventral brainstem at P7 and P21

cellular

increased oligodendrocyte number ( J:285841 )

• 2-fold increase in the number of oligodendroglial cells in the ventral brainstem at P7 and P21

Genotype
MGI:7386922

cn3

• Allelic Composition: Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Rn7sk^tm1.1Mfrye/Rn7sk^tm1.1Mfrye; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129 * C57BL/6NCrl * CBA * CD-1 * SJL

integument

abnormal epidermal layer morphology ( J:331226 )

• reduced cellularity in tamoxifen-treated mice from P4

• however, mice recover one month after the last tamoxifen application

Genotype
MGI:6296002

cn4

• Allelic Composition: Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Kras^tm4Tyj/Kras⁺; Tg(Pdx1-cre)6Tuv/0; Trp53^tm2Tyj/Trp53⁺
• Genetic Background: involves: 129 * C57BL/6NCrl * FVB/N

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:245611 )

• pancreas contains PanINs and adenocarcinoma

increased pancreatic intraepithelial neoplasia incidence ( J:245611 )

• pancreas contains PanINs and adenocarcinoma

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:245611 )

• pancreas contains PanINs and adenocarcinoma

increased pancreatic intraepithelial neoplasia incidence ( J:245611 )

• pancreas contains PanINs and adenocarcinoma

increased metastatic potential ( J:245611 )

• most mice develop metastases which are numerous and widespread in many different sites, including the lymph nodes, diaphragm, lungs, and liver

• all mice exhibit peritoneal disseminated tumor cells

Genotype
MGI:6296000

cn5

• Allelic Composition: Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Kras^tm4Tyj/Kras⁺; Prdm1^tm1Clme/Prdm1^tm1Clme; Tg(Pdx1-cre)6Tuv/0; Trp53^tm2Tyj/Trp53⁺
• Genetic Background: involves: 129 * C57BL/6NCrl * FVB/N

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:245611 )

• mice exhibit a similar overall pancreatic tumor burden as KPCT (Kras^tm4Tyj/Kras⁺ Trp53^tm2Tyj/Trp53⁺ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺) mice

• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice

• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells

• cancer cells exhibit a higher mitotic index than KPCT mice

increased pancreatic intraepithelial neoplasia incidence ( J:245611 )

• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice

mortality/aging

premature death ( J:245611 )

• mice exhibit a shorter survival than KPCT mice

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:245611 )

• mice exhibit a similar overall pancreatic tumor burden as KPCT (Kras^tm4Tyj/Kras⁺ Trp53^tm2Tyj/Trp53⁺ Tg(Pdx1-cre)6Tuv/0 Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺) mice

• pancreas contains PanINs and adenocarcinoma that are similar to pancreatic ductal adenocarcinoma (PDAC) in KPCT mice

• only 3 of 14 mice develop metastases, with only half of mice showing peritoneal disseminated tumor cells

• cancer cells exhibit a higher mitotic index than KPCT mice

increased pancreatic intraepithelial neoplasia incidence ( J:245611 )

• pancreas contains PanINs and adenocarcinoma that are similar to PDAC in KPCT mice

Genotype
MGI:5562538

cn6

• Allelic Composition: Chat^tm2(cre)Lowl/Chat⁺; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Sema6a^{Gt(KST069)Byg}/Sema6a^{Gt(KST069)Byg}
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6NCr

nervous system

abnormal inhibitory postsynaptic currents ( J:202884 )

• starburst amacrine cells in flat mount retinas show excess and aberrant light-evoked inhibitory postsynaptic currents

Genotype
MGI:5559544

cn7

• Allelic Composition: Atf5^{tm1(KOMP)Vlcg}/Atf5^{tm1(KOMP)Vlcg}; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Or4e5^tm1(cre)Rax/Or4e5⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6NCr * C57BL/6NTac

taste/olfaction

abnormal olfactory receptor morphology ( J:205214 )

• frequent olfactory receptor switching at 6 weeks

nervous system

abnormal olfactory receptor morphology ( J:205214 )

• frequent olfactory receptor switching at 6 weeks

craniofacial

abnormal olfactory receptor morphology ( J:205214 )

• frequent olfactory receptor switching at 6 weeks

respiratory system

abnormal olfactory receptor morphology ( J:205214 )

• frequent olfactory receptor switching at 6 weeks

growth/size/body

abnormal olfactory receptor morphology ( J:205214 )

• frequent olfactory receptor switching at 6 weeks

Genotype
MGI:5469877

cn8

• Allelic Composition: Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Syngap1^tm1.1Geno/Syngap1⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6 * C57BL/6NCr

nervous system

abnormal CNS synaptic transmission ( J:193208 )

• adult injection of cre-expressing virus produces an increase in intrinsic excitability of dentate gyrus neurons compared with control mice

abnormal glutamate-mediated receptor currents ( J:193208 )

• mice injected with a cre-expressing virus exhibit an increase in dentate gyrus neuron AMPA/NMDA ratio compared with control mice

Genotype
MGI:6295996

cn9

• Allelic Composition: Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Hmga2^tm1.1Mmw/Hmga2⁺; Kras^tm4Tyj/Kras⁺; Tg(Pdx1-cre)6Tuv/0; Trp53^tm2Tyj/Trp53⁺
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * C57BL/6NCrl * FVB/N

endocrine/exocrine glands

increased pancreatic ductal adenocarcinoma incidence ( J:245611 )

• mice develop pancreatic ductal adenocarcinoma (PDAC)

neoplasm

increased pancreatic ductal adenocarcinoma incidence ( J:245611 )

• mice develop pancreatic ductal adenocarcinoma (PDAC)

increased metastatic potential ( J:245611 )

• GFP+ PDAC cells form tumors form more metastases than GFP- PDAC cells when transplanted into recipient mice

• the highly metastatic PDAC subpopulation is enriched for hypoxia-induced genes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic ductal adenocarcinoma		DOID:3498		J:245611

Genotype
MGI:6192637

cn10

• Allelic Composition: Rem2^{tm1c(EUCOMM)Hmgu}/Rem2^{tm1c(EUCOMM)Hmgu}; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6N * C57BL/6NCrl
• Cell Lines: HEPD0760_4_D07

nervous system

decreased dendritic spine density ( J:263600 )

• 10 days after sparse injection with cre-expressing virus, mice exhibit decreased spine density, spine head width and spine neck length compared with control mice

Genotype
MGI:5438775

cn11

• Allelic Composition: Fgf10^{tm1.1(cre/ERT2)Sbel}/Fgf10^tm1Sms; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6

respiratory system

abnormal lung bud morphology ( J:187831 )

• with tamoxifen administration to dams from E8.5 to 14.5, embryonic lungs display abnormal shape and simplified branching (reduced number of terminal buds in accessory lobe as example)

limbs/digits/tail

interdigital webbing ( J:187831 )

• with tamoxifen administration to dams from E8.5 to 14.5, webbed digits are observed at level of forelimbs in embryos

digestive/alimentary system

abnormal cecum development ( J:187831 )

• with tamoxifen administration to dams from E8.5 to 14.5, cecum length is decreased in embryos relative to controls

Genotype
MGI:8159410

cn12

• Allelic Composition: Hmgcs2^tm1.1Yil/Hmgcs2^tm1.1Yil; Lgr5^{tm3(cre/ERT2)Cle}/Lgr5⁺; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S6/SvEvTac * C3H * C57BL/6J * C57BL/6NCrl

digestive/alimentary system

abnormal jejunal goblet cell morphology ( J:280699 )

• 12 days after a single TAM injection, mice show a significant increase in the number of mucin+ goblet cells in proximal jejunal crypts

• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of AB/PAS+ goblet cells in proximal jejunal crypts

abnormal intestinal crypt stem cell physiology ( J:280699 )

• when mice are treated with TAM 24 h prior to crypt isolation, ISCs cultured in standard medium are 34.4% less capable of forming organoids, with resulting organoids showing a 40.5% increase in goblet cells and a 64.3% decrease in tdTomato+ cells per organoid relative to controls

• exogenous beta-hydroxybutyrate (beta-OHB), but not lactate (a Paneth niche-derived metabolite that sustains ISC function), restores the organoid-forming capacity and generation of tdTomato + clones and rescues the secretory lineage bias

increased Paneth cell number ( J:280699 )

• 12 and >22 days after a single TAM injection, mice show a significant increase in the number of LYZ1+ Paneth cells in proximal jejunal crypts

• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls)

• as early 24 h after TAM injection, ISCs generate significantly greater numbers of tdTomato+ Paneth cells in jejunal sections

• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of LYZ+ Paneth cells in proximal jejunal crypts

abnormal jejunum crypts of Lieberkuhn morphology ( J:280699 )

• TAM-treated mice show a progressive loss of OLFM4+ intestinal stem cells (ISCs) and early progenitors (seen both at 10-12 days and at 17+ days but not at 5-7 days after a single TAM injection), along with an increase in the numbers of Paneth cells and goblet cells in proximal jejunal crypts

• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a modest increase in the fraction stem cells (35.34% vs 22.96% in controls), fewer transit-amplifying progenitors (18.40% vs 25.73% in controls) and a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls), along with a weakened Lgr5+ stemness signature in ISCs but only minor effects on proliferation and apoptosis

• 12 days after a single TAM injection, crypt cells show induction of Atoh1 mRNA transcripts and reduction of Hes1 mRNA transcripts by ISH

• 17 days after a single TAM injection, no change in the proliferation or apoptosis of ISCs and progenitors is observed, and small intestine length, crypt depth, and numbers of chromogranin A+ enteroendocrine cells in jejunal crypts are normal

• TAM-treated mice show reduced numbers of H3K27ac-positive and Notch intracellular domain (NICD)-positive crypt cell nuclei, indicating increased class I histone deacetylase (HDAC) activity and less Notch signaling

• TAM treatment followed by administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of H3K27ac-positive and NICD-positive crypt cell nuclei to wild-type numbers

enhanced intestine regeneration ( J:280699 )

• when mice are fed a ketogenic diet (KTD) for 4 weeks, TAM-treated and then irradiated, the number of tdTomato+ crypts per mm jejunum is significantly higher than in chow-fed control mice, indicating enhanced regenerative output of tdTomato-labeled ISCs after injury

impaired intestine regeneration ( J:280699 )

• when mice are treated with TAM 1 day prior to radiation-induced intestinal epithelial injury, ISCs generate 5-fold less labeled tdTomato+ crypts with fewer Lgr5+ ISC-derived labeled progeny extending up crypt-villous units at 5 days post-radiation, and the overall number of surviving intact jejunal crypts is reduced by 2-fold

• oral administration of poly(lactic-co-glycolic acid) (PLGA) encapsulated beta-hydroxybutyrate (beta-OHB) nanoparticles or betaOHB oligomers partially rescues intestinal regeneration after radiation-induced damage

• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) rescues the decline in ISC numbers and ISC function after radiation-induced injury

endocrine/exocrine glands

increased Paneth cell number ( J:280699 )

• 12 and >22 days after a single TAM injection, mice show a significant increase in the number of LYZ1+ Paneth cells in proximal jejunal crypts

• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls)

• as early 24 h after TAM injection, ISCs generate significantly greater numbers of tdTomato+ Paneth cells in jejunal sections

• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of LYZ+ Paneth cells in proximal jejunal crypts

abnormal jejunum crypts of Lieberkuhn morphology ( J:280699 )

• TAM-treated mice show a progressive loss of OLFM4+ intestinal stem cells (ISCs) and early progenitors (seen both at 10-12 days and at 17+ days but not at 5-7 days after a single TAM injection), along with an increase in the numbers of Paneth cells and goblet cells in proximal jejunal crypts

• 5 days after a single TAM injection, flow-sorted Lgr5+ ISC-derived tdTomato+ progeny show a modest increase in the fraction stem cells (35.34% vs 22.96% in controls), fewer transit-amplifying progenitors (18.40% vs 25.73% in controls) and a 5.8-fold increase in Paneth cells (7.88% vs 1.36% in controls), along with a weakened Lgr5+ stemness signature in ISCs but only minor effects on proliferation and apoptosis

• 12 days after a single TAM injection, crypt cells show induction of Atoh1 mRNA transcripts and reduction of Hes1 mRNA transcripts by ISH

• 17 days after a single TAM injection, no change in the proliferation or apoptosis of ISCs and progenitors is observed, and small intestine length, crypt depth, and numbers of chromogranin A+ enteroendocrine cells in jejunal crypts are normal

• TAM-treated mice show reduced numbers of H3K27ac-positive and Notch intracellular domain (NICD)-positive crypt cell nuclei, indicating increased class I histone deacetylase (HDAC) activity and less Notch signaling

• TAM treatment followed by administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of H3K27ac-positive and NICD-positive crypt cell nuclei to wild-type numbers

homeostasis/metabolism

abnormal response to radiation ( J:280699 )

• mice treated with TAM 1 day prior to radiation-induced intestinal epithelial injury show impaired Lgr5+ ISC-mediated repair in jejunal crypts relative to controls

• oral administration of nanoparticle PLGA-encapsulated beta-OHB or betaOHB oligomers partially rescues intestinal regeneration after radiation-induced damage

• when mice are fed a ketogenic diet (KTD) for 4 weeks, TAM-treated and then irradiated, the number of tdTomato+ crypts per mm jejunum is significantly higher than in chow-fed controls, indicating enhanced regenerative output of tdTomato-labeled ISCs after injury

• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) rescues the decline in ISC numbers and ISC function after radiation-induced injury

cellular

abnormal jejunal goblet cell morphology ( J:280699 )

• 12 days after a single TAM injection, mice show a significant increase in the number of mucin+ goblet cells in proximal jejunal crypts

• TAM treatment followed administration of the HDAC inhibitor quisinostat (JNJ, 1 mg/kg, 5 i.p. injections) restores the number of AB/PAS+ goblet cells in proximal jejunal crypts

abnormal intestinal crypt stem cell physiology ( J:280699 )

• when mice are treated with TAM 24 h prior to crypt isolation, ISCs cultured in standard medium are 34.4% less capable of forming organoids, with resulting organoids showing a 40.5% increase in goblet cells and a 64.3% decrease in tdTomato+ cells per organoid relative to controls

• exogenous beta-hydroxybutyrate (beta-OHB), but not lactate (a Paneth niche-derived metabolite that sustains ISC function), restores the organoid-forming capacity and generation of tdTomato + clones and rescues the secretory lineage bias

Genotype
MGI:5523454

cn13

• Allelic Composition: Gt(ROSA)26Sor^{tm1(HBEGF)Awai}/Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}; Oxt^{tm1.1(cre)Dolsn}/Oxt⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

growth/size/body

growth/size/body region phenotype ( J:192007 )

N • on a standard chow diet, 9 week-old mice given an injection of diphtheria toxin, with a second injection 1 week later, to ablate oxytocin-expressing neurons (lesioned mice), showed comparable body weight through 20 weeks of age

increased susceptibility to diet-induced obesity ( J:192007 )

♂ • when 9 week-old mice were given an injection of diphtheria toxin, with a second injection 1 week later, and maintained on a high fat diet following treatment, males displayed comparable body weight to controls up to 14 weeks of age, then develop higher body weight relative to controls at 22 weeks of age; in contrast, females show no difference in body weight compared to controls up to 22 weeks of age

adipose tissue

increased total body fat amount ( J:192007 )

• diphtheria toxin-treated males (lesioned) show significantly higher fat mass; lean masses are comparable

behavior/neurological

behavior/neurological phenotype ( J:192007 )

N • average daily food consumption measured over one week in control and lesioned (diphtheria toxin-treated) males are similar on normal chow and high fat diets

N • treatment of control and lesioned mice with MTII (melanocortin receptor agonist) reduced feeding in the dark to similar degrees in both cohorts

homeostasis/metabolism

increased susceptibility to diet-induced obesity ( J:192007 )

♂ • when 9 week-old mice were given an injection of diphtheria toxin, with a second injection 1 week later, and maintained on a high fat diet following treatment, males displayed comparable body weight to controls up to 14 weeks of age, then develop higher body weight relative to controls at 22 weeks of age; in contrast, females show no difference in body weight compared to controls up to 22 weeks of age

decreased oxygen consumption ( J:192007 )

• lesioned mice on a high fat diet show lower oxygen consumption during a 2 day period of high fat diet, particularly during the dark cycle, compared to controls; during a 2 day period on normal chow diet, oxygen consumption is comparable between the two genotypes

decreased response to leptin ( J:192007 )

• after overnight fasting, leptin administration caused a 25% reduction in 2-hour feeding in lesioned mice and had no significant effect on 4- and 24-hour feeding whereas control mice treated with leptin showed a 25% decrease in 2- and 4-hour feeding and blunted 24-hour feeding by 20%

Genotype
MGI:8159416

cn14

• Allelic Composition: Lgr5^{tm3(cre/ERT2)Cle}/Lgr5⁺; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NCrl

digestive/alimentary system

impaired intestine regeneration ( J:280699 )

• when mice are fed with a glucose-supplemented chow diet for 2 weeks and treated with TAM prior to radiation-induced intestinal injury, the ability of ISCs to generate tdTomato+ labeled progeny is reduced by 2-fold while the overall number of surviving intact jejunal crypts is significantly decreased at 3 days post-radiation

• a single oral bolus of beta-hydroxybutyrate (beta-OHB) 16 h prior to irradiation rescues these functional deficits

homeostasis/metabolism

abnormal response to radiation ( J:280699 )

• when mice are fed with a glucose-supplemented chow diet for 2 weeks and treated with TAM prior to radiation-induced intestinal injury, the ability of intestinal stem cells (ISCs) to generate tdTomato+ labeled progeny is reduced by 2-fold while the overall number of surviving intact jejunal crypts is significantly decreased at 3 days post-radiation

• a single oral bolus of beta-hydroxybutyrate (beta-OHB) 16 h prior to irradiation rescues these functional deficits

Genotype
MGI:7448866

cn15

• Allelic Composition: Mllt11^{tm1c(KOMP)Mbp}/Mllt11^{tm1c(KOMP)Mbp}; Gt(ROSA)26Sor^{tm9(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Cux2^{tm1.1(cre)Mull}/Cux2⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N

nervous system

abnormal stratification in cerebral cortex ( J:324710 )

• at E18.5, cortices show an apical shift in the expression domain of Cux2, a marker of intermediate progenitors that give rise to upper layer (UL) 2/3 cortical projection neurons (CPNs)

• however, TdTomato levels are largely normal at E14.5, E16.5 and E18.5

abnormal neurite morphology ( J:324710 )

• in culture, primary upper layer CPNs show a progressive reduction in neurite outgrowth and branching complexity