Phenotypes Associated with This Genotype

Genotype
MGI:3706574

• Allelic Composition: Ctnnb1^{tm1(Nfkbia)Rsu}/Ctnnb1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

premature death ( J:71744 )

• 50% of mutants live less than 6 months

• the maximum life span is 1 year

prenatal lethality, incomplete penetrance ( J:71744 )

• a proportion of mutants die during embryogenesis

immune system

increased leukocyte cell number ( J:71744 )

increased granulocyte number ( J:71744 )

• granulocytosis

abnormal macrophage physiology ( J:71744 )

• impaired macrophage activity

decreased Peyer's patch number ( J:71744 )

• Peyer's patches are reduced in size and numbers in 90% of mutants

small Peyer's patches ( J:71744 )

absent Peyer's patches ( J:71744 )

• Peyer's patches are absent in 10% of mutants

abnormal peripheral lymph node morphology ( J:71744 )

small axillary lymph nodes ( J:71744 )

• mutants posses only small numbers of minute axilar/brachial lymph nodes

small brachial lymph nodes ( J:71744 )

• mutants posses only small numbers of minute axilar/brachial lymph nodes

abnormal cervical lymph node morphology ( J:71744 )

• mutants have only small numbers of superficial cervical lymph nodes

absent popliteal lymph nodes ( J:71744 )

• absent draining popliteal lymph nodes

absent peripheral lymph nodes ( J:71744 )

• absent peripheral lymph nodes

increased inflammatory response ( J:71744 )

increased susceptibility to otitis media ( J:71744 )

• middle ear exhibits chronic otitis media

conjunctivitis ( J:71744 )

• after about 1 month, mutants develop conjunctivitis

keratoconjunctivitis sicca ( J:71744 )

• mutants acquire severe keratoconjunctivits sicca, due to a reduced immune response, eventually resulting in blindness

increased susceptibility to parasitic infection ( J:71744 )

• mutants infected with Leishmania major develop significantly more severe lesions than wild-type; increased infection susceptibility is caused by reduced NOS2 activity in macrophages and not by type I T-helper-cell deficiencies

vision/eye

conjunctivitis ( J:71744 )

• after about 1 month, mutants develop conjunctivitis

keratoconjunctivitis sicca ( J:71744 )

• mutants acquire severe keratoconjunctivits sicca, due to a reduced immune response, eventually resulting in blindness

abnormal eye morphology ( J:71744 )

• mutants reaching adulthood have slanted eyes

absent Meibomian glands ( J:71744 )

abnormal cornea epithelium morphology ( J:71744 )

• keratinization of the corneal epithelium is seen after 6 months of age

abnormal cornea stroma morphology ( J:71744 )

• hyperproliferation of the corneal stroma is detected after 6 months of age

narrow eye opening ( J:71744 )

• palpebral fissures are narrowed

abnormal eyelid margin morphology ( J:71744 )

• margins of the eyelids are thickened, caused by a hyperproliferative epidermis of the eyelid margin

early eyelid opening ( J:71744 )

• eyes open only after 2.5-3 weeks after birth

• however, the eye-bulb, conjunctiva, and the cornea develop normally

blindness ( J:71744 )

• blindness occurs as a result of severe keratoconjunctivitis sicca

dry eyes ( J:71744 )

• the eyes dehydrate with time due to the absence of the Meibomian glands

growth/size/body

misaligned incisors ( J:71744 )

• abnormal incisor positioning

short incisors ( J:71744 )

• incisors do not reach normal lengths in adults

small molars ( J:71744 )

• molars do not reach normal lengths in adults

growth retardation of incisors ( J:71744 )

• outgrowth of incisors is delayed

growth retardation of molars ( J:71744 )

• outgrowth of molars is delayed

decreased body size ( J:71744 )

• mutants reaching adulthood are small and thin, about 50-70% of wild-type

endocrine/exocrine glands

absent Meibomian glands ( J:71744 )

Harderian gland atrophy ( J:71744 )

• atrophy of Harderian glands

abnormal sweat gland morphology ( J:71744 )

• the sweat glands are absent in the foot pads

hearing/vestibular/ear

deafness ( J:71744 )

• hearing tests reveal deafness starting at 4-6 weeks of age

increased susceptibility to otitis media ( J:71744 )

• middle ear exhibits chronic otitis media

digestive/alimentary system

gastrointestinal hemorrhage ( J:71744 )

• lethal bleedings in the gut

abnormal intestinal goblet cell morphology ( J:71744 )

• reduction in the number of intestinal goblet cells

abnormal small intestine morphology ( J:71744 )

• the epithelial structure of the small intestine is loosened

cardiovascular system

gastrointestinal hemorrhage ( J:71744 )

• lethal bleedings in the gut

liver hemorrhage ( J:71744 )

• lethal bleedings in the liver

craniofacial

misaligned incisors ( J:71744 )

• abnormal incisor positioning

short incisors ( J:71744 )

• incisors do not reach normal lengths in adults

small molars ( J:71744 )

• molars do not reach normal lengths in adults

growth retardation of incisors ( J:71744 )

• outgrowth of incisors is delayed

growth retardation of molars ( J:71744 )

• outgrowth of molars is delayed

domed cranium ( J:71744 )

hematopoietic system

increased leukocyte cell number ( J:71744 )

increased granulocyte number ( J:71744 )

• granulocytosis

abnormal macrophage physiology ( J:71744 )

• impaired macrophage activity

homeostasis/metabolism

abnormal nitric oxide homeostasis ( J:71744 )

• reduced nitric oxide production

liver/biliary system

liver hemorrhage ( J:71744 )

• lethal bleedings in the liver

increased hepatocyte apoptosis ( J:71744 )

• livers show an increase in embryonic (E12.5-14.5) hepatocyte apoptosis

• however, mutants surviving to birth and adulthood, do not show gross liver abnormalities

reproductive system

decreased litter size ( J:71744 )

skeleton

misaligned incisors ( J:71744 )

• abnormal incisor positioning

short incisors ( J:71744 )

• incisors do not reach normal lengths in adults

small molars ( J:71744 )

• molars do not reach normal lengths in adults

growth retardation of incisors ( J:71744 )

• outgrowth of incisors is delayed

growth retardation of molars ( J:71744 )

• outgrowth of molars is delayed

domed cranium ( J:71744 )

limbs/digits/tail

abnormal foot pad morphology ( J:71744 )

• in the foot pads, plicae digitalis (deeply indented transversed folds) and sweat glands are absent

kinked tail ( J:71744 )

behavior/neurological

lethargy ( J:71744 )

tremors ( J:71744 )

impaired balance ( J:71744 )

• mutants show equilibrium problems

• however, the inner ear structure and hair cells show no abnormalities

hunched posture ( J:71744 )

integument

increased hair follicle apoptosis ( J:71744 )

• mutants exhibit an increased rate of apoptosis in many pelage follicles

absent Meibomian glands ( J:71744 )

abnormal sweat gland morphology ( J:71744 )

• the sweat glands are absent in the foot pads

abnormal coat/ hair morphology ( J:71744 )

• the only hair type found in mutants reaching adulthood is a monotrich-awl intermediate

abnormal coat appearance ( J:71744 )

• mutants reaching adulthood have shaggy fur

abnormal hair growth ( J:71744 )

• mutants reaching adulthood have no hair on the tail and behind the ears

alopecia ( J:71744 )

• patchy alopecia in older mice

abnormal hair follicle development ( J:71744 )

• hair follicles develop at a slower rate

absent hair follicles ( J:71744 )

• no anlagen for hair follicles is seen in the tail

decreased hair follicle number ( J:71744 )

• newborns produce very few hair follicles and the reduced number of hair follicles persists throughout adulthood

abnormal vibrissa follicle morphology ( J:71744 )

• mutants exhibit an increased rate of apoptosis in many vibrissal follicles

sparse vibrissae ( J:71744 )

• mutants reaching adulthood have fewer vibrissae

cellular

abnormal intestinal goblet cell morphology ( J:71744 )

• reduction in the number of intestinal goblet cells

increased hair follicle apoptosis ( J:71744 )

• mutants exhibit an increased rate of apoptosis in many pelage follicles

increased hepatocyte apoptosis ( J:71744 )

• livers show an increase in embryonic (E12.5-14.5) hepatocyte apoptosis

• however, mutants surviving to birth and adulthood, do not show gross liver abnormalities

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
otitis media		DOID:10754		J:71744