Cdkn1a<tm1Tyj> Targeted Allele Detail MGI Mouse (MGI:1933751)

Cdkn1a^tm1Tyj
Targeted Allele Detail

Nomenclature

Symbol:	Cdkn1a^tm1Tyj
Name:	cyclin-dependent kinase inhibitor 1A (P21); targeted mutation 1, Tyler Jacks
MGI ID:	MGI:1933751
Synonyms:	Cdkn1a-, p21-, p21^cip-
Gene:	Cdkn1a Location: Chr17:29227924-29237667 bp, + strand Genetic Position: Chr17, 15.23 cM

Mutation
origin

Germline Transmission:	Earliest citation of germline transmission: J:68068
Parent Cell Line:	D3 (ES Cell)
Strain of Origin:	129S2/SvPas

Mutation
description

Allele Type:	Targeted (knock-out)
Mutations:	Insertion, Intragenic deletion
	The coding sequences were replaced by a neomycin cassette. No protein was detected by immunoprecipitation of ES cell lysates in which both alleles were disrupted. (J:68068)
Inheritance:	Recessive

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 2 strains available Cell Lines: 0 lines available
Carrying any Cdkn1a Mutation:	40 strains or lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	hm1	hm2	hm3	cn4	cn5	cx6	tg7
cellular			√				N
cellular phenotype							N
increased sensitivity to induced cell death			√
increased cellular sensitivity to ultraviolet irradiation			√
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
endocrine/exocrine glands						√		√
abnormal mammary gland growth during lactation						√
abnormal Harderian gland morphology								√
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
growth/size							N
growth/size phenotype							N
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
hearing/vestibular/ear		N
hearing/vestibular/ear phenotype		N
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
hematopoietic system					√			√
decreased thymocyte number					√
extramedullary hematopoiesis								√
enlarged spleen								√
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
homeostasis/metabolism				√
increased incidence of chemically-induced tumors				√
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
immune system					√			√
immune system phenotype					N
decreased thymocyte number					√
enlarged spleen								√
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
muscle							N
muscle phenotype							N
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
reproductive system						√
abnormal mammary gland growth during lactation						√
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
tumorigenesis				√				√
increased tumor incidence								√
increased incidence of chemically-induced tumors				√
mammary adenocarcinoma								√
salivary adenocarcinoma								√
		hm1	hm2	hm3	cn4	cn5	cx6	tg7
vision/eye								√
abnormal Harderian gland morphology								√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	B6;129S2-Cdkn1a^tm1Tyj/J
hearing/vestibular/ear hearing/vestibular/ear phenotype (J:98518) contrary to expectation, homozygotes display a normal inner ear morphology relative to wild-type mice at E16.5, E18.5, P2 and 2 months of age, no significant differences in the cytoarchitecture of vestibular and auditory sensory epithelia or aberrant mitoses in developing hair cells are observed
Genotype	Allelic Composition	Genetic Background
hm2	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	involves: 129S2/SvPas
cellular increased sensitivity to induced cell death (J:85569) mutant MEFs are more sensitive to etoposide, adriamycin, or cisplatin induced apoptosis than wild-type MEFs increased cellular sensitivity to ultraviolet irradiation (J:85569) MEFs are highly sensitive to UV-induced apoptosis
Genotype	Allelic Composition	Genetic Background
hm3	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj	involves: 129S2/SvPas * C57BL/6
tumorigenesis increased incidence of chemically-induced tumors (J:80271) treatment with the chemical carcinogen, urethane, results in accelerated tumor onset and increased tumor multiplicity compared to controls; tumors are predominantly lung tumors homeostasis/metabolism increased incidence of chemically-induced tumors (J:80271) treatment with the chemical carcinogen, urethane, results in accelerated tumor onset and increased tumor multiplicity compared to controls; tumors are predominantly lung tumors
Genotype	Allelic Composition	Genetic Background
cn4	Brca1^tm2Mak/Brca1^tm2Mak Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Tg(Lck-cre)548Jxm/?	involves: 129P2/OlaHsd * C57BL/6 * CBA
immune system immune system phenotype (J:63282) T cell numbers in lymph nodes are more nearly normal decreased thymocyte number (J:63282) hematopoietic system decreased thymocyte number (J:63282)
Genotype	Allelic Composition	Genetic Background
cn5	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Itgb1^tm1Mll/Itgb1^tm1Mll Tg(Wap-cre)1Gsc/0	involves: 129S2/SvPas * C57BL/6 * FVB/N
endocrine/exocrine glands abnormal mammary gland growth during lactation (J:99405) mutants show a decrease in cell proliferation in mammary glands compared to wild-type, however they show a significant increase in cell proliferation compared to the conditional Itgb1 mutant glands, which represents a partial, 55%, reversion of the phenotype reproductive system abnormal mammary gland growth during lactation (J:99405) mutants show a decrease in cell proliferation in mammary glands compared to wild-type, however they show a significant increase in cell proliferation compared to the conditional Itgb1 mutant glands, which represents a partial, 55%, reversion of the phenotype
Genotype	Allelic Composition	Genetic Background
cx6	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Foxk1^tm1Djg/Foxk1^tm1Djg	involves: 129S2/SvPas * 129S4/SvJae
cellular cellular phenotype (J:81688) G₀/G₁ arrest of cell cycle is prevented growth/size growth/size phenotype (J:81688) growth retardation is prevented there is no significant size difference from controls muscle muscle phenotype (J:81688) no impairment in skeletal muscle regeneration is observed
Genotype	Allelic Composition	Genetic Background
tg7	Cdkn1a^tm1Tyj/Cdkn1a^tm1Tyj Tg(MMTV-vHaras)SH1Led/0	involves: 129S2/SvPas * C57BL/6J * CD-1 * FVB/N
tumorigenesis increased tumor incidence (J:66183) exhibit earlier onset of tumors and increased tumor multiplicity and aggressiveness, however, once tumors appear, their growth rate, apoptosis level, and mitotic index are not affected mammary adenocarcinoma (J:66183) by 63 days of age, all mice develop either malignant (mammary and/or salivary adenocarcinomas) or benign (Harderian hyperplasia) tumors, compared to only 1 of 9 controls expressing only the Tg(MMTV-vHaras)SH1Led transgene by 94 days of age, 50% develop mammary tumors compared to none of the controls by 4 months of age, the mammary tumor multiplicity is 10-fold greater than in controls salivary adenocarcinoma (J:66183) by 63 days of age, all mice develop either malignant (mammary and/or salivary adenocarcinomas) or benign (Harderian hyperplasia) tumors, compared to only 1 of 9 controls expressing only the Tg(MMTV-vHaras)SH1Led transgene endocrine/exocrine glands abnormal Harderian gland morphology (J:66183) 100% of mutants exhibit bilateral hyperplasia of the Harderian lacrimal glands by 63 days of age enlargement of the glands is evident as early as 5 weeks after birth, with glands reaching up to 20 times their normal weight by 4 months of age hematopoietic system extramedullary hematopoiesis (J:66183) extramedullary hematopoiesis, frequently displaying atypical lymphoid cells and megakariocytes, results in splenomegaly enlarged spleen (J:66183) splenomegaly is due to a moderate to marked extramedullary hematopoiesis immune system enlarged spleen (J:66183) splenomegaly is due to a moderate to marked extramedullary hematopoiesis vision/eye abnormal Harderian gland morphology (J:66183) 100% of mutants exhibit bilateral hyperplasia of the Harderian lacrimal glands by 63 days of age enlargement of the glands is evident as early as 5 weeks after birth, with glands reaching up to 20 times their normal weight by 4 months of age

References

Original:	J:68068 Brugarolas J et al., "Radiation-induced cell cycle arrest compromised by p21 deficiency." Nature 1995 Oct 12;377(6549):552-7
All:	90 reference(s)

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