Phenotypes associated with this allele

• Allele Symbol: Xpc^tm1Brd
• Allele Name: targeted mutation 1, Allan Bradley
• Allele ID: MGI:1931883
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Xpc^tm1Brd/Xpc^tm1Brd	involves: 129S7/SvEvBrd * C57BL	MGI:3665144
cx2	Ercc6^tm1Gvh/Ercc6^tm1Gvh Xpc^tm1Brd/Xpc^tm1Brd	involves: 129P2/OlaHsd * 129S7/SvEvBrd	MGI:5319078
cx3	Mc1r^e/Mc1r^e Xpc^tm1Brd/Xpc^tm1Brd Tg(KRT14-Kitl)1Takk/0	involves: 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3686788

Genotype
MGI:3665144

hm1

• Allelic Composition: Xpc^tm1Brd/Xpc^tm1Brd
• Genetic Background: involves: 129S7/SvEvBrd * C57BL

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

neoplasm

increased incidence of tumors by UV-induction ( J:28708 )

• highly susceptible to ultraviolet-induced carcinogenesis; predominantly form squamous cell carcinomas around the ears

• do not exhibit an increased susceptibility to spontaneous tumor generation at one year of age

vision/eye

photosensitivity ( J:28708 )

• ultraviolet irradiation produces frequent eye abnormalities including severe keratitis and corneal ulceration which are not found in controls

cellular

abnormal cell physiology ( J:28708 )

• MEFs show a significant decrease in the ability to form colonies compared to wild-type on exposure to ultraviolet light

homeostasis/metabolism

photosensitivity ( J:28708 )

• ultraviolet irradiation produces frequent eye abnormalities including severe keratitis and corneal ulceration which are not found in controls

integument

increased sensitivity to skin irradiation ( J:28708 )

• ultraviolet-irradiated mutants show marked hyperplasia of the epidermis with focal areas of hyperkeratosis and varying degrees of dysplasia, acantholysis and/or dyskeratosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
xeroderma pigmentosum group C		DOID:0110844	OMIM:278720	J:28708

Genotype
MGI:5319078

cx2

• Allelic Composition: Ercc6^tm1Gvh/Ercc6^tm1Gvh; Xpc^tm1Brd/Xpc^tm1Brd
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd

mortality/aging

lethality at weaning, complete penetrance ( J:182229 )

• mutants die around P21

growth/size/body

cachexia ( J:182229 )

• mutants exhibit whole-body wasting

postnatal growth retardation ( J:182229 )

• mutants fail to thrive and show a 50% reduction in body weight at death

behavior/neurological

limb grasping ( J:182229 )

• abnormal clasping reflex and complete inactivity upon tail suspension

ataxia ( J:182229 )

impaired coordination ( J:182229 )

• on the rotarod, mutants are unable to stay on the rotating beam

abnormal gait ( J:182229 )

• mutants exhibit deficits in the catwalk gait analysis test, with shorter stride lengths than controls and reduced base of support in both the front and hind paws

short stride length ( J:182229 )

nervous system

abnormal myelin sheath morphology ( J:182229 )

• mutants exhibit widespread reduction of myelin basic protein (MBP) and myelin in the sensorimotor cortex, the stratum radiatum, the corpus callosum, and the anterior commissure

abnormal oligodendrocyte physiology ( J:182229 )

• oligodendrocytes appear to exhibit normal proliferation and differentiation, however they are unable to generate sufficient MBP or to maintain the proper myelination during early development, indicating that they may not mature into MBP-synthesizing cells

abnormal myelination ( J:182229 )

• mutants exhibit hypomyelination in the anterior commissure and corpus callosum due to dysmyelination and not demyelination

• reduction in both the number of myelinated axons and the average diameter of myelin surrounding the axons

Genotype
MGI:3686788

cx3

• Allelic Composition: Mc1r^e/Mc1r^e; Xpc^tm1Brd/Xpc^tm1Brd; Tg(KRT14-Kitl)1Takk/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * SJL

growth/size/body

weight loss ( J:112959 )

• vehicle-treated mutants show weight loss, indicative of failure to thrive, compared to forskolin-treated animals

neoplasm

increased tumor incidence ( J:112959 )

• vehicle-treated mutant controls develop tumors more rapidly (11 tumors ~4 weeks after 20 weeks of UV-B exposure) compared to forskolin-treated mice (6 tumors, onset ~25 weeks)

• other types of tumors are found in vehicle-treated mice (3/11); 2/9 mice develop multiple tumors

increased squamous cell carcinoma incidence ( J:112959 )

• tumors in vehicle-treated mutants are mainly this type (6/11) while forskolin-treated mice develop only this type

integument

thick epidermis ( J:112959 )

• vehicle-treated mutants show significant sun damage after 20 weeks of UV-B exposure including profound epidermal thickening while forskoling treatment prevented damage

skin lesions ( J:112959 )

• vehicle-treated mutants show evidence of sun damage like scarring after 20 weeks of UV-B exposure while forskolin treatment prevented damage