Phenotypes Associated with This Genotype

Genotype
MGI:2174786

• Allelic Composition: Trp73^tm1Fmc/Trp73^tm1Fmc
• Genetic Background: involves: 129S4/SvJae

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:60896 )

• Background Sensitivity: at weaning, homozygotes of a mixed (unspecified) genetic background exhibit about a 50% reduction in postnatal survival relative to wild-type littermates; postnatal survival is further reduced to less than 25% on a predominantly 129 genetic background

immune system

increased susceptibility to otitis media ( J:60896 )

• pre-weaning homozygotes exhibit severe purulent otitis media, with massive neutrophil infiltrates and mucosecretions detected as early as P2

• in adulthood, >80% of homozygotes display chronic otitis media

chronic inflammation ( J:60896 )

• adult homozygotes exhibit chronic infections and inflammation

conjunctivitis ( J:60896 )

• in adulthood, >80% of homozygotes display conjunctivitis

rhinitis ( J:60896 )

• pre-weaning homozygotes exhibit severe purulent rhinitis, with massive neutrophil infiltrates and mucosecretions detected as early as P2

• in adulthood, >80% of homozygotes display chronic, bilateral rhinitis

sinus inflammation ( J:60896 )

• at P2, homozygotes exhibit massive sinus inflammation, characterized by mucoserous secretions, neutrophil infiltrates, goblet cell hyperplasia of the surrounding epithelia but absence of obvious Gram-staining pathogens

increased susceptibility to bacterial infection ( J:60896 )

• in adulthood (but not earlier), homozygotes contain E. coli, P. aerogenes and micrococcal species in affected sites; however, lymphoid and granulocyte populations remain normal

nervous system

intracranial hemorrhage ( J:60896 )

• homozygotes exhibit intracranial hemorrhage in ~15% of mortalities

intraventricular hemorrhage ( J:60896 )

abnormal vomeronasal organ morphology ( J:60896 )

• in homozygotes, the vomeronasal organ, an accessory olfactory struture involved in pheromone detection, lacks pheromone receptors V1R and V2R as well as expression of the olfactory cell adhesion molecule (OCAM), suggesting abnormal pheromone sensory pathways and loss of pheromone responses

absent Cajal-Retzius cell ( J:60896 )

• homozygotes show absence of Cajal-Retzius cells in the cortical marginal zone and hippocampal molecular layer; however, no cortical lamination defect is observed

hydrocephaly ( J:60896 )

• homozygotes exhibit a mild, congenital hydrocephalus

non-obstructive hydrocephaly ( J:60896 )

• some homozygotes display a highly morbid form of communicating hydrocephalus, marked by severely expanded lateral ventricles, a compressed cortex and intraventricular hemorrhage

dilated lateral ventricle ( J:60896 )

abnormal hippocampus morphology ( J:180144 )

abnormal hippocampus development ( J:60896 )

• homozygotes exhibit hippocampal dysgenesis, as shown by aberrant arrangements of the CA1-CA3 pyramidal cells layer and the dentate gyrus

• in contrast, the neocortex and cerebellum appear unaffected

abnormal hippocampus CA3 region morphology ( J:180144 )

• mossy fiber and polysialylated neural cell adhesion molecule-positive projections are shorter in the CA3 region

abnormal dentate gyrus morphology ( J:60896 , J:180144 )

• the mutant dentate gyrus lacks an infrapyramidal blade while the suprapyramidal blade is hypertrophic and extended (J:60896)

• hippocampal neurons in the dentate gyrus show a disorganized distribution and altered morphology (J:180144)

abnormal hippocampal mossy fiber morphology ( J:180144 )

• mossy fiber projections in the CA3 region are reduced in length

abnormal hippocampus neuron morphology ( J:180144 )

• hippocampal neurons in the dentate gyrus show a disorganized distribution and altered morphology

• neurons have a reduced number of branches and shorter dendrites

abnormal dendrite morphology ( J:180144 )

• cultured DIV 5 cortical neurons show a significant reduction in the number of branches resulting in a decrease in dendritic tree complexity

abnormal cerebrospinal fluid production ( J:60896 )

• the presence of non-obstructive hydrocephalus in some homozygotes indicates possible defects in the production or reabsorption of CSF

hearing/vestibular/ear

increased susceptibility to otitis media ( J:60896 )

• pre-weaning homozygotes exhibit severe purulent otitis media, with massive neutrophil infiltrates and mucosecretions detected as early as P2

• in adulthood, >80% of homozygotes display chronic otitis media

digestive/alimentary system

gastrointestinal hemorrhage ( J:60896 )

• most commonly, homozygotes display massive gastrointestinal hemorrhages followed by death

absent enterocytes ( J:60896 )

• at P7, homozygotes display an absence of enterocytes

distended ileum ( J:60896 )

• at P7, homozygotes display a distended and eroded ileum

excessive digestive secretion ( J:60896 )

• at P7, homozygotes exhibit excessive mucosecetion in the duodenum, ileum and cecum

cardiovascular system

gastrointestinal hemorrhage ( J:60896 )

• most commonly, homozygotes display massive gastrointestinal hemorrhages followed by death

intracranial hemorrhage ( J:60896 )

• homozygotes exhibit intracranial hemorrhage in ~15% of mortalities

intraventricular hemorrhage ( J:60896 )

growth/size/body

abnormal vomeronasal organ morphology ( J:60896 )

• in homozygotes, the vomeronasal organ, an accessory olfactory struture involved in pheromone detection, lacks pheromone receptors V1R and V2R as well as expression of the olfactory cell adhesion molecule (OCAM), suggesting abnormal pheromone sensory pathways and loss of pheromone responses

periorbital edema ( J:60896 )

• in adulthood, >80% of homozygotes display periorbital edema

decreased body size ( J:60896 )

• homozygous mutant pups display runting

cachexia ( J:60896 )

• at P7, homozygotes display features of wasting, such as excessive digestive mucosecretion

respiratory system

abnormal vomeronasal organ morphology ( J:60896 )

• in homozygotes, the vomeronasal organ, an accessory olfactory struture involved in pheromone detection, lacks pheromone receptors V1R and V2R as well as expression of the olfactory cell adhesion molecule (OCAM), suggesting abnormal pheromone sensory pathways and loss of pheromone responses

rhinitis ( J:60896 )

• pre-weaning homozygotes exhibit severe purulent rhinitis, with massive neutrophil infiltrates and mucosecretions detected as early as P2

• in adulthood, >80% of homozygotes display chronic, bilateral rhinitis

sinus inflammation ( J:60896 )

• at P2, homozygotes exhibit massive sinus inflammation, characterized by mucoserous secretions, neutrophil infiltrates, goblet cell hyperplasia of the surrounding epithelia but absence of obvious Gram-staining pathogens

vision/eye

conjunctivitis ( J:60896 )

• in adulthood, >80% of homozygotes display conjunctivitis

craniofacial

domed cranium ( J:60896 )

• at weaning, homozygotes display domed crania associated with expansion of ventricles, compression of the cortex and intracranial hemorrhaging

abnormal vomeronasal organ morphology ( J:60896 )

• in homozygotes, the vomeronasal organ, an accessory olfactory struture involved in pheromone detection, lacks pheromone receptors V1R and V2R as well as expression of the olfactory cell adhesion molecule (OCAM), suggesting abnormal pheromone sensory pathways and loss of pheromone responses

periorbital edema ( J:60896 )

• in adulthood, >80% of homozygotes display periorbital edema

skeleton

domed cranium ( J:60896 )

• at weaning, homozygotes display domed crania associated with expansion of ventricles, compression of the cortex and intracranial hemorrhaging

homeostasis/metabolism

periorbital edema ( J:60896 )

• in adulthood, >80% of homozygotes display periorbital edema

behavior/neurological

submission towards male mice ( J:60896 )

• male homozygotes lack aggressive responses towards other males

reduced male mating frequency ( J:60896 )

♂ • male homozygotes lack interest in sexually mature females

reproductive system

female infertility ( J:60896 )

♀ • matings of female homozygotes with wild-type males fail to result in pregnancies, indicating a defect in conceiving or maintaining embryos

neoplasm

neoplasm ( J:60896 )

N • homozygotes aged 2-15 months show no increased susceptibility to spontaneous tumorigenesis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
otitis media		DOID:10754		J:60896