All Phenotypes Wwox<tm1Ria> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Wwox^tm1Ria/Wwox^tm1Ria	involves: 129X1/SvJ * C57BL/6	MGI:3706959
hm2	Wwox^tm1Ria/Wwox^tm1Ria	involves: 129X1/SvJ * C57BL/6J	MGI:3842217
ht3	Wwox^tm1Ria/Wwox⁺	involves: 129X1/SvJ * C57BL/6	MGI:3706961

Allelic Composition	Wwox^tm1Ria/Wwox^tm1Ria
Genetic Background	involves: 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Wwox^tm1Ria mutation (0 available); any Wwox mutation (59 available)

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

Tumor phenotype in Wwox^tm1Ria/Wwox^tm1Ria mice

mortality/aging

premature death ( J:120064 )

• mice die by 4 weeks of age

neoplasm

increased osteosarcoma incidence ( J:120064 )

• 4 of 13 mice examined had focal lesions along with dysplasia that appeared neoplastic, one each at age day 3 and 5 and 2 mice at age 2.5 week

• tumor motphology suggests these are either periosteal or chondroid osteosarcomas

• lesions contain enlarged cells in the cartilage matrix with multiple nucleoli

skeleton

increased osteosarcoma incidence ( J:120064 )

• 4 of 13 mice examined had focal lesions along with dysplasia that appeared neoplastic, one each at age day 3 and 5 and 2 mice at age 2.5 week

• tumor motphology suggests these are either periosteal or chondroid osteosarcomas

• lesions contain enlarged cells in the cartilage matrix with multiple nucleoli

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

Impaired growth and decreased bone density in Wwox^tm1Ria/Wwox^tm1Ria mice

mortality/aging

postnatal lethality, complete penetrance ( J:138140 )

• 100% die at 2-3 weeks of age

growth/size/body

decreased body size ( J:138140 )

cachexia ( J:138140 )

• atrophy of many organs without significant microscopic lesions

postnatal growth retardation ( J:138140 )

• pups grow more slowly than control littermates

skeleton

abnormal osteoclast physiology ( J:138140 )

• increase in osteoclast activity in the primary spongiosa under the growth plate on P3 and osteoclasts on nearly all trabeculae on P5

abnormal skeleton morphology ( J:138140 )

• mutants develop metabolic bone disease

decreased bone mineral density ( J:138140 )

• osteopenia

decreased compact bone thickness ( J:138140 )

• thinner cortical bone in the diaphysis

abnormal trabecular bone morphology ( J:138140 )

• decrease in density of trabeculae bone is observed beginning at 7 days after birth

abnormal skeleton development ( J:138140 )

• delay in postnatal bone formation due to a defect in differentiation beginning at the mineralization stage

• decrease in bone formation

abnormal osteoblast differentiation ( J:138140 )

• osteoblast differentiation is impaired at the mature osteoblast stage (beginning at E12)

increased bone resorption ( J:138140 )

homeostasis/metabolism

abnormal homeostasis ( J:146986 )

• altered gene expression of key steroidogenesis enzymes in mutant testis and ovary, including enzymes of the cytochrome P450 family

increased blood uric acid level ( J:138140 )

increased circulating bilirubin level ( J:138140 )

hypoglycemia ( J:138140 )

decreased circulating testosterone level ( J:146986 )

• serum testosterone levels are undetectable

decreased circulating cholesterol level ( J:138140 )

decreased circulating triglyceride level ( J:138140 )

decreased circulating calcium level ( J:138140 )

• 50% reduction in serum calcium

increased circulating phosphate level ( J:138140 )

• 20% increase in serum phosphate levels

increased circulating potassium level ( J:138140 )

decreased circulating sodium level ( J:138140 )

abnormal circulating enzyme level ( J:138140 )

• increase in serum levels of the liver enzyme gamma-glutamyl transpeptidase (GGT)

decreased circulating alkaline phosphatase level ( J:138140 )

decreased circulating aspartate transaminase level ( J:138140 )

• decrease in serum levels of aspartate aminotransferase (AST)

decreased circulating serum albumin level ( J:138140 )

decreased circulating total protein level ( J:138140 )

decreased circulating chloride level ( J:138140 )

endocrine/exocrine glands

increased adrenal gland weight ( J:138140 )

• adrenal gland is heavier

increased pituitary gland weight ( J:138140 )

• pituitary gland is heavier

abnormal primary ovarian follicle morphology ( J:146986 )

• mutant primary follicles are significantly smaller than wild-type

decreased theca cell number ( J:146986 )

• mutant ovaries exhibit reduced theca cell proliferation, as revealed by Ki-67 staining

small ovary ( J:146986 )

small seminiferous tubules ( J:146986 )

• mutant seminiferous tubules are significantly smaller than wild-type and contain immature germ cells

decreased Leydig cell number ( J:146986 )

• a sparse interstitium and very few Leydig cells of decreased size are observed

• expression of key Leydig cell markers, including two fetal markers, is reduced indicating a decreased number of fetal Leydig cells in juvenile mutant testes

small testis ( J:146986 )

testis hypoplasia ( J:146986 )

abnormal pituitary gland physiology ( J:146986 )

• FSH and, to a lesser extent, LH expression is down-regulated in mutant pituitary glands

immune system

abnormal osteoclast physiology ( J:138140 )

• increase in osteoclast activity in the primary spongiosa under the growth plate on P3 and osteoclasts on nearly all trabeculae on P5

nervous system

increased pituitary gland weight ( J:138140 )

• pituitary gland is heavier

abnormal pituitary gland physiology ( J:146986 )

• FSH and, to a lesser extent, LH expression is down-regulated in mutant pituitary glands

increased brain weight ( J:138140 )

• brain is heavier

reproductive system

abnormal primary ovarian follicle morphology ( J:146986 )

• mutant primary follicles are significantly smaller than wild-type

decreased theca cell number ( J:146986 )

• mutant ovaries exhibit reduced theca cell proliferation, as revealed by Ki-67 staining

small ovary ( J:146986 )

small seminiferous tubules ( J:146986 )

• mutant seminiferous tubules are significantly smaller than wild-type and contain immature germ cells

decreased Leydig cell number ( J:146986 )

• a sparse interstitium and very few Leydig cells of decreased size are observed

• expression of key Leydig cell markers, including two fetal markers, is reduced indicating a decreased number of fetal Leydig cells in juvenile mutant testes

small testis ( J:146986 )

testis hypoplasia ( J:146986 )

thin uterine horn ( J:146986 )

cellular

abnormal osteoblast differentiation ( J:138140 )

• osteoblast differentiation is impaired at the mature osteoblast stage (beginning at E12)

hematopoietic system

abnormal osteoclast physiology ( J:138140 )

• increase in osteoclast activity in the primary spongiosa under the growth plate on P3 and osteoclasts on nearly all trabeculae on P5

Allelic Composition	Wwox^tm1Ria/Wwox⁺
Genetic Background	involves: 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Wwox^tm1Ria mutation (0 available); any Wwox mutation (59 available)

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

Tumor phenotype in Wwox^tm1Ria/Wwox⁺ mice

neoplasm

increased tumor incidence ( J:120064 )

• 5-fold increase in tumor incidence and in number of tumors per mouse compared to wild-type mice

• mice develop multiple types of spontaneous tumors including liver hemangioma and lymphoma infiltrations in the internal organs not seen in wild-type mice

• spontaneous tumors with increased incidence include centroblastic lymphoma (10%) and Burkitts cell lymphoma (5%)

• however, the incidence of spontaneous large cell lymphomas is the same as in wild-type

increased incidence of tumors by chemical induction ( J:120064 )

• ENU-induced (20 mg/kg) tumor incidence isincreased to 80% compared to 48% in wild-type mice

• ENU treated heterozygotes have increased lung cancer incidence (72%) lymphoma incidence (59%) and incidence of other tumors (20%) compared to treated wild-type mice (36%, 31%, and 2.4%, respectively)

• ENU-induced lung tumor multiplicity (83) and lymphoma aggressiveness (63) are increased compared to treated wild-type mice (31 and 32, respectively)

• a number of other tumors are found only in ENU-treated heterozygotes including liver hemangiomas (11%), chondrosarconmas (2%), fibroadenomas (2%), squamous cell carcinomas (4%) and lymphoma infiltrate in internal organs, mainly livers and lungs (9%)

increased lung tumor incidence ( J:120064 )

• incidence of spontaneous lung papillary carcinomas is 15.5% compared to 3.3% in wild-type mice

hematopoietic system

enlarged spleen ( J:120064 )

• 59% of ENU-treated heterozygotes present with enlarged spleens compared to 31% in treated wild-type with the presence of atypia of the malignant lymphoblasts

• proliferating lymphocytes were largely B220+/IgM+ B cells

immune system

enlarged spleen ( J:120064 )

• 59% of ENU-treated heterozygotes present with enlarged spleens compared to 31% in treated wild-type with the presence of atypia of the malignant lymphoblasts

• proliferating lymphocytes were largely B220+/IgM+ B cells

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:120064 )

• ENU-induced (20 mg/kg) tumor incidence isincreased to 80% compared to 48% in wild-type mice

• ENU-induced lung tumor multiplicity (83) and lymphoma aggressiveness (63) are increased compared to treated wild-type mice (31 and 32, respectively)

respiratory system

increased lung tumor incidence ( J:120064 )

• incidence of spontaneous lung papillary carcinomas is 15.5% compared to 3.3% in wild-type mice

growth/size/body

enlarged spleen ( J:120064 )

• 59% of ENU-treated heterozygotes present with enlarged spleens compared to 31% in treated wild-type with the presence of atypia of the malignant lymphoblasts

• proliferating lymphocytes were largely B220+/IgM+ B cells

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support.	last database update 11/19/2024 MGI 6.24