Phenotypes associated with this allele

• Allele Symbol: Dicer1^tm1Snj
• Allele Name: targeted mutation 1, Stephen N Jones
• Allele ID: MGI:3809260
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dicer1^tm1Snj/Dicer1^tm1Snj	involves: 129S7/SvEvBrd * C57BL/6	MGI:3809296
cn2	Dicer1^tm1Snj/Dicer1^tm1Snj	involves: 129S7/SvEvBrd * C57BL/6	MGI:3809298
cn3	Dicer1^tm1Snj/Dicer1^tm1Snj Trp53^tm1Brn/Trp53^+ Tg(KRT5-cre/PGR)1Der/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR	MGI:5618124
cn4	Dicer1^tm1Snj/Dicer1^tm1Snj Trp53^tm1Brn/Trp53^tm1Brn Tg(KRT5-cre/PGR)1Der/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR	MGI:5618123
cn5	Dicer1^tm1Snj/Dicer1^tm1Snj Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S7/SvEvBrd * C57BL/6	MGI:3809304
cn6	Dicer1^tm1Snj/Dicer1^tm1Snj Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3809305
cn7	Dicer1^tm1Snj/Dicer1^tm1Snj Tg(KRT5-cre/PGR)1Der/0	involves: 129S7/SvEvBrd * C57BL/6 * FVB * ICR	MGI:3809306
cn8	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Dicer1^tm1Snj/Dicer1^tm1Snj	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3809301
cx9	Dicer1^tm1Snj/Dicer1^tm1Snj Trp53^tm1Brd/Trp53^tm1Brd	involves: 129S7/SvEvBrd * C57BL/6	MGI:3809302
cx10	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Dicer1^tm1Snj/Dicer1^tm1Snj	involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3809300

Genotype
MGI:3809296

hm1

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

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

normal phenotype

no abnormal phenotype detected ( J:139257 )

• mice are indistinguishable from wild-type mice

Genotype
MGI:3809298

cn2

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cellular

abnormal cell physiology ( J:139257 )

• mouse embryonic fibroblasts transfected with an adenovirus cre fail to produce micro RNAs and exhibit increased DNA damage that leads to premature senescence

abnormal mitosis ( J:139257 )

• mouse embryonic fibroblasts transfected with an adenovirus cre exhibit an increase in the number of cells in S phase

decreased cell proliferation ( J:139257 )

• mouse embryonic fibroblasts transfected with an adenovirus cre cell proliferation is slowed compared to in wild-type cells

early cellular replicative senescence ( J:139257 )

• mouse embryonic fibroblasts transfected with an adenovirus cre exhibit premature senescence associated with increased DNA damage

decreased DNA replication ( J:139257 )

• mouse embryonic fibroblasts transfected with an adenovirus cre undergo less DNA replication than in wild-type cells

homeostasis/metabolism

decreased DNA replication ( J:139257 )

• mouse embryonic fibroblasts transfected with an adenovirus cre undergo less DNA replication than in wild-type cells

Genotype
MGI:5618124

cn3

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Trp53^tm1Brn/Trp53⁺; Tg(KRT5-cre/PGR)1Der/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR

mortality/aging

premature death ( J:216813 )

• mean survival is 13 months, with none surviving beyond 18 months

• lethality before 1 year is unrelated to cancer as no tumors are seen until after 1 year of age

integument

increased skin tumor incidence ( J:216813 )

• mice that survive beyond 1 year of age develop skin tumors

• less than 1/4 of mice develop more than a single tumor

increased basal cell carcinoma incidence ( J:216813 )

• mice form mostly basal cell carcinomas

neoplasm

increased skin tumor incidence ( J:216813 )

• mice that survive beyond 1 year of age develop skin tumors

• less than 1/4 of mice develop more than a single tumor

increased basal cell carcinoma incidence ( J:216813 )

• mice form mostly basal cell carcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
basal cell carcinoma		DOID:2513		J:216813

Genotype
MGI:5618123

cn4

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(KRT5-cre/PGR)1Der/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6N * FVB/N * ICR

mortality/aging

premature death ( J:216813 )

• mean survival is 9 months

integument

progressive hair loss ( J:216813 )

• loss of fur by the 5th week of age, with mice nearly devoid of fur and whiskers by 12 weeks of age

abnormal hair shaft morphology ( J:216813 )

abnormal hair follicle morphology ( J:216813 )

• dysmorphic hair follicles with dyskertotic cells in the follicular epithelium

• regions of increased cellularity with many mitotic figures are seen in the interfollicular epidermal layer and above the basal layer

• large amount of DNA damage in the basal layer of follicular epithelium and in the interfollicular epidermis

• there is some evidence of attempts to form new follicles

abnormal hair cycle ( J:216813 )

• at a time when control hair follicles are in the telogen phase of the hair cycles, mutants show anagen growth phase hairs with dysmorphic follicles, abnormal hair shafts, and dyskertotic cells in the follicular epithelium

abnormal epidermis stratum basale morphology ( J:216813 )

• pre-malignant basaloid proliferation is seen

hypergranulosis ( J:216813 )

thick epidermis ( J:216813 )

• increase in thickness of the epidermis with a mean thickness of 51.3 um compared to 24 um in controls

increased skin tumor incidence ( J:216813 )

• mice develop highly aggressive and numerous skin tumors starting at 7-8 months of age with all mice showing skin tumors by 12-15 months of age

• 41% of mice form multiple tumors

increased skin squamous cell carcinoma incidence ( J:216813 )

• mice form moderately or poorly differentiated squamous cell carcinomas and nearly half of mutants develop poorly differentiated carcinomas

• poorly or undifferentiated carcinomas are highly invasive

abnormal skin physiology ( J:216813 )

• the number of apoptotic cells in the epidermis is lower than in single conditional Dicer1 mutants

• increase in the numbers of mitotic cells in the epidermis, indicating increased proliferation

neoplasm

increased skin tumor incidence ( J:216813 )

• mice develop highly aggressive and numerous skin tumors starting at 7-8 months of age with all mice showing skin tumors by 12-15 months of age

• 41% of mice form multiple tumors

increased skin squamous cell carcinoma incidence ( J:216813 )

• mice form moderately or poorly differentiated squamous cell carcinomas and nearly half of mutants develop poorly differentiated carcinomas

• poorly or undifferentiated carcinomas are highly invasive

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
squamous cell carcinoma		DOID:1749		J:216813

Genotype
MGI:3809304

cn5

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Trp53^tm1Brd/Trp53^tm1Brd
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cellular

cellular phenotype ( J:139257 )

N • mouse embryonic fibroblasts treated with an adenovirus cre exhibit normal cellular senescence

Genotype
MGI:3809305

cn6

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CBA

limbs/digits/tail

abnormal limb development ( J:139257 )

• at E14 to E16, tamoxifen treated mice exhibit increased cellular senescence in developing limbs compared to in wild-type mice

Genotype
MGI:3809306

cn7

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Tg(KRT5-cre/PGR)1Der/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * FVB * ICR

mortality/aging

premature death ( J:216813 )

• mice die as early as 6 months of age, with a mean survival of 16 months and 80% dying by 20 months of age

integument

alopecia ( J:139257 )

• at 2 to 3 months of age

progressive hair loss ( J:216813 )

• mice begin to lose their fur and whiskers shortly after the 5th week of age, by 10 weeks of age, mice only retain small patches of fur and are devoid of any fur at 3 months of age

abnormal hair follicle morphology ( J:216813 )

• interfollicular epidermis exhibits an increase in cellularity

• large amount of DNA damage in the basal layer of follicular epithelium and in the interfollicular epidermis

decreased hair follicle number ( J:216813 )

hair follicle degeneration ( J:216813 )

• hair follicles are debris-laden and mis-oriented and enlarged cells and apoptotic figures are seen surrounding the degraded follicle structure

loss of vibrissae ( J:216813 )

• mice begin to lose their whiskers shortly after the 5th week of age, by 10 weeks of age, mice show only a few misshapen whiskers, and mice are devoid of whiskers at 3 months of age

abnormal epidermal layer morphology ( J:139257 , J:216813 )

• at 2 to 3 months of age, mice exhibit a roughening of the epidermis (J:139257)

• cells are larger than in wild-type mice and display a senescence phenotype (J:139257)

• mice exhibit a roughened epidermis at 3 months of age (J:216813)

• interfollicular epidermis exhibits an increase in cellularity (J:216813)

thick epidermis ( J:216813 )

• increase in thickness of the epidermis with a mean thickness of 42 um compared to 24 um in controls

abnormal skin physiology ( J:216813 )

• increase in the numbers of apoptotic cells in the epidermis

• increase in the numbers of mitotic cells in the epidermis, indicating increased proliferation

growth/size/body

cachexia ( J:216813 )

• several mutants exhibit mild cachexia before death

neoplasm

neoplasm ( J:216813 )

N • no tumors are seen upon death

Genotype
MGI:3809301

cn8

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Dicer1^tm1Snj/Dicer1^tm1Snj
• Genetic Background: involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL

cellular

cellular phenotype ( J:139257 )

N • mouse embryonic fibroblasts treated with an adenovirus cre exhibit normal cellular senescence

Genotype
MGI:3809302

cx9

• Allelic Composition: Dicer1^tm1Snj/Dicer1^tm1Snj; Trp53^tm1Brd/Trp53^tm1Brd
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cellular

increased cell proliferation ( J:139257 )

Genotype
MGI:3809300

cx10

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Dicer1^tm1Snj/Dicer1^tm1Snj
• Genetic Background: involves: 129/Sv * 129S7/SvEvBrd * C57BL/6 * SJL

cellular

increased cell proliferation ( J:139257 )