Phenotypes associated with this allele

• Allele Symbol: Csnk1a1^tm1.1Ybn
• Allele Name: targeted mutation 1.1, Yinon Ben-Neriah
• Allele ID: MGI:5543667
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.2Ybn	involves: 129 * BALB/c * C57BL/6 * CD-1	MGI:5543690
cn2	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129 * C57BL/6 * CD-1 * DBA/2	MGI:5543691
cn3	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0 Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * C57BL/6 * CD-1 * DBA/2	MGI:5543693
cn4	Csnk1a1^tm1.1Ybn/Csnk1a1^+ Tg(Vil1-cre/ERT2)23Syr/0 Trp53^tm1Brn/Trp53^tm1Brn	involves: 129 * C57BL/6 * CD-1 * DBA/2	MGI:5543694
cn5	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129 * C57BL/6 * CD-1 * DBA/2	MGI:5543696
cn6	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Trp53^tm1Brn/Trp53^tm1Brn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:6448982
cn7	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT14-cre/ERT)20Efu/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * CD-1	MGI:6246565
cn8	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0 Trp53^tm3.1Tyj/Trp53^tm3.1Tyj	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2	MGI:6448987
cn9	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Trp53^tm2.1Tyj/Trp53^tm2.1Tyj Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * 129X1/SvJ * 129S4/SvJae * C57BL/6 * DBA/2	MGI:6448984
cn10	Crbn^tm1.1Ble/Crbn^tm1.1Ble Csnk1a1^tm1.1Ybn/Csnk1a1^+ Tg(Mx1-cre)1Cgn/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:6280334
cn11	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:6448985
cn12	Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(KRT14-cre/ERT)20Efu/0	involves: 129S1/Sv * 129X1/SvJ * CD-1	MGI:6246562

Genotype
MGI:5543690

ht1

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.2Ybn
• Genetic Background: involves: 129 * BALB/c * C57BL/6 * CD-1

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

mortality/aging

mortality/aging ( J:204886 )

N • mice live a full lifespan without development of tumorigenesis

neoplasm

neoplasm ( J:204886 )

N • mice life a full lifespan without development of tumorigenesis

Genotype
MGI:5543691

cn2

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1 * DBA/2

cellular

increased apoptosis ( J:204886 )

• in the gut following tamoxifen treatment

increased fibroblast apoptosis ( J:204886 )

• in mouse embryonic fibroblasts following tamoxifen treatment

Genotype
MGI:5543693

cn3

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * C57BL/6 * CD-1 * DBA/2

mortality/aging

premature death ( J:204886 )

• after 2 weeks of tamoxifen treatment

neoplasm

increased carcinoma incidence ( J:204886 )

• widespread high-grade dysplasia and numerous intramucosal carcinomas invading the lamina propria in most of the small-bowel crypts and villi within 2 weeks of tamoxifen treatment

digestive/alimentary system

abnormal enterocyte proliferation ( J:204886 )

• increased proliferation after tamoxifen treatment throughout the crypt-villus axis

cellular

increased apoptosis ( J:204886 )

• in the gut of tamoxifen treated mice but no more so than in Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(Vil-cre/ERT2)23Syr mice

abnormal enterocyte proliferation ( J:204886 )

• increased proliferation after tamoxifen treatment throughout the crypt-villus axis

Genotype
MGI:5543694

cn4

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1⁺; Tg(Vil1-cre/ERT2)23Syr/0; Trp53^tm1Brn/Trp53^tm1Brn
• Genetic Background: involves: 129 * C57BL/6 * CD-1 * DBA/2

neoplasm

increased carcinoma incidence ( J:204886 )

• within 6 months, 7 of 9 tamoxifen-treated mice develop invasive carcinomas that permeates the bowel muscular wall into the subserosal fat with some involvement of the serosal surface (stage T4)

Genotype
MGI:5543696

cn5

• Allelic Composition: Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj; Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129 * C57BL/6 * CD-1 * DBA/2

neoplasm

increased carcinoma incidence ( J:204886 )

• tamoxifen-treated mice exhibit severe dysplasia and intramucosal carcinomas throughout the small bowel

digestive/alimentary system

abnormal enterocyte proliferation ( J:204886 )

• massive proliferation in the villi compartment in tamoxifen-treated mice

cellular

abnormal enterocyte proliferation ( J:204886 )

• massive proliferation in the villi compartment in tamoxifen-treated mice

Genotype
MGI:6448982

cn6

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the entire bowel

• distal gut dysplasia appears later than in mice with Trp53^tm2.1Tyj (containing the R172H missense mutation)

abnormal intestine development ( J:291671 )

• jejunal and ileal organoids exhibit increased proliferation, decreased differentiation, and resemble highly dysplastic spheroids

abnormal enterocyte morphology ( J:291671 )

• high-grade dysplasia in the entire bowel

abnormal jejunum crypts of Lieberkuhn morphology ( J:291671 )

• enlarged and dysplastic

endocrine/exocrine glands

abnormal jejunum crypts of Lieberkuhn morphology ( J:291671 )

• enlarged and dysplastic

cellular

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the entire bowel

• distal gut dysplasia appears later than in mice with Trp53^tm2.1Tyj (containing the R172H missense mutation)

Genotype
MGI:6246565

cn7

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * CD-1

Skin hyperpigmentation in Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(KRT14-cre/ERT)20Efu/0 mice but not in Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT14-cre/ERT)20Efu/0 mice

integument

abnormal epidermal layer morphology ( J:253611 )

• after tamoxifen i.p. treatment, the epidermis becomes dysplastic with no melanin deposition

abnormal epidermis stratum basale morphology ( J:253611 )

• at day 28 after tamoxifen i.p. treatment, BrdU+ (proliferating) cells and beta-catenin nuclear staining are increased in the basal layer of the epidermis; however, most of the positive cells are multinucleated clumping cells indicating abnormal mitoses associated with epidermal dysplasia

pigmentation

pigmentation phenotype ( J:253611 )

N • mice do NOT develop skin hyperpigmentation after tamoxifen i.p. treatment

N • melanin is mainly distributed in the dermis and less in the epidermis, similar to control mice

Genotype
MGI:6448987

cn8

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0; Trp53^tm3.1Tyj/Trp53^tm3.1Tyj
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

abnormal enterocyte morphology ( J:291671 )

• dysplastic in the colon and ileum, but not the duodenum and jejunum

cellular

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

Genotype
MGI:6448984

cn9

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Trp53^tm2.1Tyj/Trp53^tm2.1Tyj; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * 129S4/SvJae * C57BL/6 * DBA/2

digestive/alimentary system

digestive/alimentary phenotype ( J:291671 )

N • jejunal and ileal organoids exhibit normal organoid differentiation and proliferation

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

• treatment of organoids with gallic acid a reversible increase in proliferation of enterocytes unlike in untreated cells that exhibit normal organoid differentiation and proliferation

• however, antibiotic treatment to eliminate gut bacteria rescues hyperproliferation proliferation defect

abnormal enterocyte morphology ( J:291671 )

• dysplastic in the colon and ileum, but not the duodenum and jejunum

• distal gut dysplasia appears earlier than in mice with null Trp53

• mice treated with gallic acid exhibit high-grade dysplastic foci unlike untreated mice\

• however, antibiotic treatment to eliminate gut bacteria results in shorter crypts and better organized villi

cellular

abnormal enterocyte proliferation ( J:291671 )

• increased proliferation in the colon and ileum, but not the duodenum and jejunum

• treatment of organoids with gallic acid a reversible increase in proliferation of enterocytes unlike in untreated cells that exhibit normal organoid differentiation and proliferation

• however, antibiotic treatment to eliminate gut bacteria rescues hyperproliferation proliferation defect

Genotype
MGI:6280334

cn10

• Allelic Composition: Crbn^tm1.1Ble/Crbn^tm1.1Ble; Csnk1a1^tm1.1Ybn/Csnk1a1⁺; Tg(Mx1-cre)1Cgn/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:267091 )

• hematopoietic stem and progenitor cells are more sensitive to lenalidomide in culture than cells from Csnk1a1^tm1.1Ybn/+ Tg(Mx1-cre)1Cgn mice

Genotype
MGI:6448985

cn11

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

digestive/alimentary system

abnormal jejunum crypts of Lieberkuhn morphology ( J:291671 )

• enlarged and dysplastic

endocrine/exocrine glands

abnormal jejunum crypts of Lieberkuhn morphology ( J:291671 )

• enlarged and dysplastic

Genotype
MGI:6246562

cn12

• Allelic Composition: Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * CD-1

Csnk1a1^tm1.1Ybn/Csnk1a1^tm1.1Ybn Tg(KRT14-cre/ERT)20Efu/0 mice show skin hyperpigmentation of ears, paws, mouth, and trunk after tamoxifen treatment

pigmentation

abnormal epidermal pigmentation ( J:253611 )

• increased melanin content in the ear epidermis at day 28 after topical 4-hydroxytamoxife (4HT) induction

• increased melanin content in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

abnormal epidermal melanocyte morphology ( J:253611 )

• a slow but significant increase of melanocyte numbers is noted in the tail epidermis during the first 14 days after topical 4HT induction, followed by a rapid increase thererafter; however, the number of dermal melanocytes is not significantly altered

• after topical 4HT induction, epidermal melanocytes become progressively larger and more dendritic, indicating melanocytic differentiation

• many dendritic melanocytes containing black melanin pigment are observed around p53+ keratinocytes at day 28 after tamoxifen i.p. treatment

• melanocyte number is increased in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

• treatment of 4HT-induced mice with oral imatinib (a Kit inhibitor) results in decreased melanocyte numbers in the epidermis at day P28 relative to vehicle-treated control mice

• intradermal injection of ACK2 (a Kit-neutralizing antibody) reduces the number of melanocytes in the epidermis at days 7 and 14 after 4HT induction relative to vehicle-treated control mice

increased melanocyte number ( J:253611 )

• a slow but significant increase of melanocyte numbers is noted in the tail epidermis during the first 14 days after topical 4HT induction, followed by a rapid increase thererafter

• melanocyte number is increased in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

• treatment of 4HT-induced mice with oral imatinib (a Kit inhibitor) results in decreased melanocyte numbers in the epidermis at day P28 relative to vehicle-treated control mice

• intradermal injection of ACK2 (a Kit-neutralizing antibody) reduces the number of melanocytes in the epidermis at days 7 and 14 after 4HT induction relative to vehicle-treated control mice

abnormal eumelanosome eumelanin content ( J:253611 )

• amount of eumelanin is significantly increased in the epidermis at day 28 after topical 4HT induction

• treatment of tamoxifen-injected mice with oral imatinib (a Kit inhibitor) results in severe reduction of eumelanin production relative to vehicle-treated control mice at day 28

• amount of pheomelanin remains unchanged during topical 4HT induction

hyperpigmentation ( J:253611 )

• at 1 month after tamoxifen i.p. treatment, mice show skin hyperpigmentation on the ears, paws, tail, mouth, and trunk relative to heterozygous control mice

• skin hyperpigmentation is accompanied by beta-catenin and p53 stabilization, preferential induction of p53 target genes, and p53-dependent up-regulation of Kit ligand

• treatment with ACK2 (a Kit-neutralizing antibody) or imatinib (a Kit inhibitor) abolishes the induction of hyperpigmentation, indicating that it requires the KitL/Kit pathway

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

increased foot pigmentation ( J:253611 )

• hyperpigmentation of the paws at 1 month after tamoxifen i.p. treatment

increased tail pigmentation ( J:253611 )

• hyperpigmentation of the tail at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the tail, esp. at >3 weeks after induction

integument

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

abnormal epidermis stratum basale morphology ( J:253611 )

• at day 28 after tamoxifen i.p. treatment, BrdU+ (proliferating) cells and beta-catenin nuclear staining are increased in the basal layer of the epidermis

epidermal hyperplasia ( J:253611 )

• after tamoxifen i.p. treatment, the epidermis becomes hyperplastic with increased melanin deposition

• treatment of tamoxifen-injected mice with oral imatinib (a Kit inhibitor) induces thinning of the epidermis with decreased melanin levels in the epidermis relative to vehicle-treated control mice

thick epidermis ( J:253611 )

• increased epidermal thickness in the ears 28 days after topical 4HT induction

abnormal epidermal pigmentation ( J:253611 )

• increased melanin content in the ear epidermis at day 28 after topical 4-hydroxytamoxife (4HT) induction

• increased melanin content in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

abnormal epidermal melanocyte morphology ( J:253611 )

• a slow but significant increase of melanocyte numbers is noted in the tail epidermis during the first 14 days after topical 4HT induction, followed by a rapid increase thererafter; however, the number of dermal melanocytes is not significantly altered

• after topical 4HT induction, epidermal melanocytes become progressively larger and more dendritic, indicating melanocytic differentiation

• many dendritic melanocytes containing black melanin pigment are observed around p53+ keratinocytes at day 28 after tamoxifen i.p. treatment

• melanocyte number is increased in the dorsal epidermis at day 28 after tamoxifen i.p. treatment

• treatment of 4HT-induced mice with oral imatinib (a Kit inhibitor) results in decreased melanocyte numbers in the epidermis at day P28 relative to vehicle-treated control mice

• intradermal injection of ACK2 (a Kit-neutralizing antibody) reduces the number of melanocytes in the epidermis at days 7 and 14 after 4HT induction relative to vehicle-treated control mice

increased foot pigmentation ( J:253611 )

• hyperpigmentation of the paws at 1 month after tamoxifen i.p. treatment

increased tail pigmentation ( J:253611 )

• hyperpigmentation of the tail at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the tail, esp. at >3 weeks after induction

abnormal skin physiology ( J:253611 )

• tamoxifen-injected mice show induction of the DNA-damage response, as shown by increased gamma-H2AX staining in the epidermis

cellular

decreased cellular sensitivity to ultraviolet irradiation ( J:253611 )

• 24 h after exposure to a high, sunburn-inducing dose of UVB, hyperpigmented tails of tamoxifen-treated mice show absence of skin swelling and significantly fewer TUNEL+ apoptotic keratinocytes in the tail skin than similarly-treated control mice, indicating protection from UV (sunburn) damage

increased apoptosis ( J:253611 )

• tamoxifen-injected mice show increased apoptosis in the epidermis, as shown by increased cleaved-caspase 3 expression

neoplasm

neoplasm ( J:253611 )

N • no skin tumor formation is observed for at least 9 months after tamoxifen i.p. treatment

growth/size/body

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

craniofacial

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

hearing/vestibular/ear

increased ear pigmentation ( J:253611 )

• hyperpigmentation of the ears at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the ear, esp. at >3 weeks after induction

limbs/digits/tail

increased tail pigmentation ( J:253611 )

• hyperpigmentation of the tail at 1 month after tamoxifen i.p. treatment

• topical treatment with 4HT for 14 days induces skin hyperpigmentation on the tail, esp. at >3 weeks after induction