Phenotypes Associated with This Genotype

Genotype
MGI:3842217

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

• ♀: 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