Phenotypes associated with this allele

• Allele Symbol: Xpa^tm1Tnka
• Allele Name: targeted mutation 1, Kiyoji Tanaka
• Allele ID: MGI:2183931
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Xpa^tm1Tnka/Xpa^tm1Tnka	C3.Cg-Xpa^tm1Tnka	MGI:4361118
hm2	Xpa^tm1Tnka/Xpa^tm1Tnka	involves: C57BL/6 * CBA	MGI:4361117
cx3	Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpa^tm1Tnka/Xpa^tm1Tnka	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:4361119
cx4	Hr^hr/Hr^hr Msh2^tm1Htr/Msh2^tm1Htr Xpa^tm1Tnka/Xpa^tm1Tnka	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:4429631
cx5	Hr^hr/Hr^hr Xpa^tm1Tnka/Xpa^tm1Tnka	involves: C57BL/6 * CBA	MGI:4429632
cx6	Xpa^tm1Tnka/Xpa^tm1Tnka Tg(KRT14-Kitl)1Takk/?	involves: C57BL/6 * CBA * SJL	MGI:4361120

Genotype
MGI:4361118

hm1

• Allelic Composition: Xpa^tm1Tnka/Xpa^tm1Tnka
• Genetic Background: C3.Cg-Xpa^tm1Tnka

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

neoplasm

increased liver tumor incidence ( J:76206 )

• significantly increased incidence of spontaneous tumors

increased liver adenoma incidence ( J:76206 )

• aflatoxin B1 induces 2-6 fold higher numbers of hepatocellular adenomas

liver/biliary system

increased liver tumor incidence ( J:76206 )

• significantly increased incidence of spontaneous tumors

increased liver adenoma incidence ( J:76206 )

• aflatoxin B1 induces 2-6 fold higher numbers of hepatocellular adenomas

Genotype
MGI:4361117

hm2

• Allelic Composition: Xpa^tm1Tnka/Xpa^tm1Tnka
• Genetic Background: involves: C57BL/6 * CBA

respiratory system

increased lung adenoma incidence ( J:62877 )

• treatment with benzo(a)pyrene by intratracheal instillation leads to lung adenomas in 71% of homozygotes compared to 35% of controls

increased lung adenocarcinoma incidence ( J:62877 )

• in 10% of mice after treatment with benzo(a)pyrene by intratracheal instillation

growth/size/body

decreased body weight ( J:141237 )

• the weight of males up to 2 years of age is reduced relative to that of controls

cellular

increased cellular sensitivity to ultraviolet irradiation ( J:28709 , J:35054 )

• fibroblasts from newborn mice are highly sensitive to UV radiation (J:28709)

• higher inflammatory edema after UV-B exposure (J:28709)

• skin ulcers form within 1-2 weeks of exposure (J:28709)

• mice develop stronger and longer lasting ear swelling/inflammatory edema after ultraviolet B (UV-B) and topical psoralen plus ultraviolet A (PUVA) radiation indicating increased susceptibility to UV-B and PUVA radiation (J:35054)

• abdominal skin shows intracellular edema and necrosis in the epidermis and subepidermal bullae at 24 hours after UV-B irradiation and mice show marked inflammatory infiltrates of lymphocytes, pronounced edema, vasodilation, and extravasation of erythrocytes in the dermis (J:35054)

• mice develop enhanced sunburn cell formation after UV-B irradiation (J:35054)

abnormal base-excision repair ( J:28709 )

• defect in nucleotide excision repair

• failure to remove thymine dimers

neoplasm

increased tumor incidence ( J:141237 )

• spontaneous tumors begin to appear at around 12 months

• spontaneous tumors are very abundant at 24 months

increased skin squamous cell carcinoma incidence ( J:28709 )

• in all mice by 34 weeks after UV-B exposure

increased lung adenoma incidence ( J:62877 )

• treatment with benzo(a)pyrene by intratracheal instillation leads to lung adenomas in 71% of homozygotes compared to 35% of controls

increased lung adenocarcinoma incidence ( J:62877 )

• in 10% of mice after treatment with benzo(a)pyrene by intratracheal instillation

increased papilloma incidence ( J:28709 )

• as a result of exposure to 9,10-dimethyl-1,2benz(a)anthracene (DMBA)

increased incidence of induced tumors ( J:28709 )

increased incidence of tumors by chemical induction ( J:28709 )

• increased sensitivity to the tumor forming effects of 9,10-dimethyl-1,2benz(a)anthracene (DMBA)

increased incidence of tumors by UV-induction ( J:28709 )

immune system

increased NK cell number ( J:55739 )

abnormal immune system physiology ( J:35054 )

• UV-B-induced local immunosuppression and UV-B-induced systemic immunosuppression are enhanced when mice are sensitized with DNFB after UV-B irradiation

• however, mice develop contact sensitivity to DNFB similarly to controls

abnormal lymphocyte physiology ( J:55739 )

• daily UV-B exposure for 3 or 5 days results in a significantly reduced cell count

• slower recovery

abnormal NK cell physiology ( J:55739 )

• daily UV-B exposure for 3 or 5 days results in a significantly reduced cell count

• cell activity reduced to significantly below non irradiated levels by 1 day after exposure

• slower recovery

• reduced activity persists at least 5 days

• full recovery of activity by day 10

abnormal Langerhans cell physiology ( J:35054 )

• mice show a greater loss of and morphologic damage of ADPase (+) Langerhans cells after UV-B irradiation

• recovery of Langerhans cells after UV-B irradiation is slower than for controls

reproductive system

abnormal testis morphology ( J:141237 )

♂

abnormal seminiferous tubule epithelium morphology ( J:141237 )

♂ • disorganization by 12 months

seminiferous tubule degeneration ( J:141237 )

♂ • some degeneration seen at 6 months

♂ • by 12 months half of tubules have vacuoles in the spermatogenic epithelium

increased Leydig cell number ( J:141237 )

♂ • at 24 months

decreased testis weight ( J:141237 )

♂ • relative testis weight drops progressively over time

♂ • down to 1/3 the weight of testes from control mice at 2 years

abnormal spermatogenesis ( J:141237 )

♂ • in all seminiferous tubules by 24 months

abnormal epididymis morphology ( J:141237 )

♂ • lack spermatozoa at 24 months

reduced male fertility ( J:141237 )

♂ • males remain fertile until about 30 weeks

homeostasis/metabolism

abnormal base-excision repair ( J:28709 )

• defect in nucleotide excision repair

• failure to remove thymine dimers

increased circulating follicle stimulating hormone level ( J:141237 )

• in males at 24 months

increased prostaglandin level ( J:60201 )

• PGD2, PGE2 and PGF2alpha levels increase significantly after UV-B irradiation

increased incidence of tumors by chemical induction ( J:28709 )

• increased sensitivity to the tumor forming effects of 9,10-dimethyl-1,2benz(a)anthracene (DMBA)

hematopoietic system

increased NK cell number ( J:55739 )

abnormal lymphocyte physiology ( J:55739 )

• daily UV-B exposure for 3 or 5 days results in a significantly reduced cell count

• slower recovery

abnormal NK cell physiology ( J:55739 )

• daily UV-B exposure for 3 or 5 days results in a significantly reduced cell count

• cell activity reduced to significantly below non irradiated levels by 1 day after exposure

• slower recovery

• reduced activity persists at least 5 days

• full recovery of activity by day 10

endocrine/exocrine glands

abnormal testis morphology ( J:141237 )

♂

abnormal seminiferous tubule epithelium morphology ( J:141237 )

♂ • disorganization by 12 months

seminiferous tubule degeneration ( J:141237 )

♂ • some degeneration seen at 6 months

♂ • by 12 months half of tubules have vacuoles in the spermatogenic epithelium

increased Leydig cell number ( J:141237 )

♂ • at 24 months

decreased testis weight ( J:141237 )

♂ • relative testis weight drops progressively over time

♂ • down to 1/3 the weight of testes from control mice at 2 years

integument

increased skin squamous cell carcinoma incidence ( J:28709 )

• in all mice by 34 weeks after UV-B exposure

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
xeroderma pigmentosum group A		DOID:0110843	OMIM:278700	J:35054

Genotype
MGI:4361119

cx3

• Allelic Composition: Ercc6^tm1Gvh/Ercc6^tm1Gvh; Xpa^tm1Tnka/Xpa^tm1Tnka
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

mortality/aging

postnatal lethality, complete penetrance ( J:72574 )

• die around 21 days of age

growth/size/body

slow postnatal weight gain ( J:72574 )

• low body weight and size develop after birth

• 40% weight reduction at 2 weeks of age

behavior/neurological

limb grasping ( J:72574 )

• clasp hind limbs when suspended by the tail

tremors ( J:72574 )

ataxia ( J:72574 )

• starting around 1 week of age

• clearly evident at 2 weeks of age

impaired balance ( J:72574 )

• sit with hind limbs spread for balance

• fall down often

abnormal gait ( J:72574 )

• walk with a wide gait

• "waltzing" locomotion

nervous system

decreased cerebellar granule cell precursor proliferation ( J:72574 )

• fewer proliferating external granular cells at 8 days

• significantly increased number of apoptotic cells

abnormal cerebellum development ( J:72574 )

reduced cerebellar foliation ( J:72574 )

• impaired foliation and sulcus formation

decreased brain weight ( J:72574 )

• 20% brain weight reduction at 2 weeks of age

abnormal cerebellar cortex morphology ( J:72574 )

abnormal cerebellar Purkinje cell layer ( J:72574 )

• thin

abnormal Purkinje cell dendrite morphology ( J:72574 )

• dendritic trees are reduced in length

thin cerebellar granule layer ( J:72574 )

thin cerebellar molecular layer ( J:72574 )

small cerebellum ( J:72574 )

• becomes strikingly small

• normal at birth

cellular

decreased cerebellar granule cell precursor proliferation ( J:72574 )

• fewer proliferating external granular cells at 8 days

• significantly increased number of apoptotic cells

Genotype
MGI:4429631

cx4

• Allelic Composition: Hr^hr/Hr^hr; Msh2^tm1Htr/Msh2^tm1Htr; Xpa^tm1Tnka/Xpa^tm1Tnka
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

mortality/aging

increased mortality induced by ionizing radiation ( J:79734 )

• 32% of mice die 15 weeks after UVB-irradiation compared with 3% of similarly treated Xpa^tm1Tnka homozygotes

premature death ( J:79734 )

• 18% of mice die of lymphomas by 20 weeks of age

neoplasm

increased skin tumor incidence ( J:79734 )

• in 81% of mice by 52 weeks

increased skin papilloma incidence ( J:79734 )

• 9% of spontaneous skin tumors are papillomas

increased skin squamous cell carcinoma incidence ( J:79734 )

• 91% of skin tumors are squamous cell carcinomas

• all skin tumors in UVB-treated mice are diagnosed as squamous cell carcinomas

increased lymphoma incidence ( J:79734 )

• 18% of mice die of lymphomas by 20 weeks of age

increased incidence of tumors by UV-induction ( J:79734 )

• UVB-treated mice develop skin tumors a week earlier than similarly treated Xpa^tm1Tnka homozygotes

• all UVB-treated mice develop skin tumors, all of which are squamous cell carcinomas, at 10 weeks compared with 20 weeks for similarly treated Xpa^tm1Tnka homozygotes

integument

increased skin tumor incidence ( J:79734 )

• in 81% of mice by 52 weeks

increased skin papilloma incidence ( J:79734 )

• 9% of spontaneous skin tumors are papillomas

increased skin squamous cell carcinoma incidence ( J:79734 )

• 91% of skin tumors are squamous cell carcinomas

• all skin tumors in UVB-treated mice are diagnosed as squamous cell carcinomas

homeostasis/metabolism

increased mortality induced by ionizing radiation ( J:79734 )

• 32% of mice die 15 weeks after UVB-irradiation compared with 3% of similarly treated Xpa^tm1Tnka homozygotes

Genotype
MGI:4429632

cx5

• Allelic Composition: Hr^hr/Hr^hr; Xpa^tm1Tnka/Xpa^tm1Tnka
• Genetic Background: involves: C57BL/6 * CBA

neoplasm

increased skin tumor incidence ( J:79734 )

• after 20 weeks, 100% of UVB-irradiated mice develop skin tumors

integument

increased skin tumor incidence ( J:79734 )

• after 20 weeks, 100% of UVB-irradiated mice develop skin tumors

Genotype
MGI:4361120

cx6

• Allelic Composition: Xpa^tm1Tnka/Xpa^tm1Tnka; Tg(KRT14-Kitl)1Takk/?
• Genetic Background: involves: C57BL/6 * CBA * SJL

pigmentation

abnormal coat/hair pigmentation ( J:100608 )

• black hair

abnormal epidermal pigmentation ( J:100608 )

• black skin

neoplasm

increased skin tumor incidence ( J:100608 )

• mice irradiated with UV-B 3X/week for 10 weeks, total dose 150J/cm²

• unevenly pigmented macules appear on re-epithelialized skin at 4 months after UV-B exposure

• lentigo maligna melanomas eventually become elevated tumors

• black nodular melanomas in some mice by 6 months after exposure

• at 53 weeks, 8 of 61 mice with nodular melanomas and 12 of 61 mice show lintigo maligna melanoma

• one type of tumor or the other, never both

increased metastatic potential ( J:100608 )

• melanoma cells invade the dermis

• both types of melanomas become metastatic

integument

abnormal coat/hair pigmentation ( J:100608 )

• black hair

abnormal epidermal pigmentation ( J:100608 )

• black skin

increased skin tumor incidence ( J:100608 )

• mice irradiated with UV-B 3X/week for 10 weeks, total dose 150J/cm²

• unevenly pigmented macules appear on re-epithelialized skin at 4 months after UV-B exposure

• lentigo maligna melanomas eventually become elevated tumors

• black nodular melanomas in some mice by 6 months after exposure

• at 53 weeks, 8 of 61 mice with nodular melanomas and 12 of 61 mice show lintigo maligna melanoma

• one type of tumor or the other, never both

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
skin melanoma		DOID:8923	OMIM:608035 OMIM:612263	J:100608