Mouse Genome Informatics
cn
    Ikbkaptm1Id/Ikbkaptm1.1Id
Tg(Hsp70-1-cre)6Arge/0

involves: 129S1/Sv * C57BL/6 * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• trimming litter size at birth allows 5% of mutants to survive postnatally
• of 6 surviving adults, 4 had to be sacrificed before 18 months of age and 2 survived to 22 months but with serious health problems, including ataxic gait, reduced locomotion activity, kyphosis and severe weight loss
• all pups die during the first postnatal days from starvation as they fail to suck milk or swallow efficiently
• trimming litter size at birth allows 5% of mutants to survive postnatally

growth/size
• mutant pups have almost no fat content at death
• mutants surviving to over 11 months of age display very little fat content
• mutants exhibit a reduction in the total number of fungiform papillae on the tongue at P18 compared with control littermates
• although fungiform papillae have a well-developed taste bud, their distribution, especially in the anterior portion of the tongue, is more sparse, and some of them do not appear healthy and are smaller than in controls
• majority of pups are born with about 70% the weight and size of their control littermates
• majority of pups are born with about 70% the weight and size of their control littermates
• at P18-P21, mutants are approximately 32% the weight of wild-type littermates
• mutants over 11 months of age display low body weight
• mutants over 11 months of age are short in length (about 85-90% the length of control littermates)
• starting at mid-gestation, embryos have a reduced growth rate

behavior/neurological
• newborn pups lack milk in stomachs
• poor sucking and uncoordinated swallow at birth
• adult mutants exhibit self-inflicted wounds from frequent scratching
• adult mutants exhibit excessive grooming, self-inflicted wounds from frequent scratching
• hindlimb clasping on tail suspension in mutants surviving to adulthood
• P18-P21 mutants exhibit postural instability
• mutants surviving to adulthood exhibit an abnormal postural behavior (sitting-up) not observed in controls, most likely to compensate for the kyphoscoliosis
• P18-P21 mutants exhibit poor locomotor coordination
• ataxic gait in mutants surviving to adulthood
• P18-P21 mutants exhibit unsteady gait
• mutants exhibit decreased temperature perception, with mutants staying on a hot plate at higher temperatures than controls
• however, the discomfort caused by temperature perception tests leads to an exaggerated nocifensive response in mutants, with mutants jumping high multiple times and this behavior persists after the noxious stimulus has ceased, unlike in controls, indicating that while mutants show decreased temperature perception, they show exaggerated responses once they feel the pain
• handling-induced seizures in mutants surviving to adulthood
• loud startling noise induced seizures in mutants that survive to adulthood

digestive/alimentary system
• mutants exhibit a reduction in the total number of fungiform papillae on the tongue at P18 compared with control littermates
• although fungiform papillae have a well-developed taste bud, their distribution, especially in the anterior portion of the tongue, is more sparse, and some of them do not appear healthy and are smaller than in controls
• mutant pups exhibit bubbles of air in their intestines at P13 indicating intestinal dysfunction

embryogenesis
• placenta growth is impaired, averaging 55% the size of wild-type placenta in embryos from mid-gestation onwards
• spongiotrophoblast layer is poorly developed at late gestation
• however the labyrinthine zone appears normal
• placenta is small and thin at E16.5

adipose tissue
• mutant pups have almost no fat content at death
• mutants surviving to over 11 months of age display very little fat content

craniofacial
• mutants exhibit a reduction in the total number of fungiform papillae on the tongue at P18 compared with control littermates
• although fungiform papillae have a well-developed taste bud, their distribution, especially in the anterior portion of the tongue, is more sparse, and some of them do not appear healthy and are smaller than in controls

immune system
• 66.7% of mutants exhibit blepharoptosis and conjunctivitis with increasing age

limbs/digits/tail
• mutants exhibit puffy feet at P18

nervous system
• handling-induced seizures in mutants surviving to adulthood
• loud startling noise induced seizures in mutants that survive to adulthood
• decrease in volume of sympathetic ganglia at birth (45% of controls)
• at E18.5, fetuses show a significant reduction in the volume of stellate ganglia compared to controls
• at E18.5, fetuses show a significant reduction in the volume of superior cervical sympathetic ganglia (SCG) compared to controls
• however, localization and differentiation of sympathetic neurons in superior cervical, stellate, and celiac ganglia are normal and neuronal density and neuronal numbers are not reduced at E18.5
• decrease in the convergence of retinal ganglion cells to the optic nerve in 22 month old mutants
• urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 5 out of 17 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some (J:188923)
• decrease in volume of the dorsal root ganglion (45% of controls)
• at 18 months of age, relative proportion of small dark B cells in lumbar dorsal root ganglia is extremely reduced compared to controls

renal/urinary system
• urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 5 out of 17 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some (J:188923)
• urine retention/neurogenic bladder and/or hydronephrosis is seen in 5 out of 17 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some (J:188923)
• urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 5 out of 17 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some (J:188923)

skeleton
• 100% of mutants surviving to adulthood develop skeletal abnormalities, mostly kyphosis or kyphoscoliosis that worsens over time

vision/eye
• 66.7% of mutants exhibit blepharoptosis and conjunctivitis with increasing age
• decrease in the convergence of retinal ganglion cells to the optic nerve in 22 month old mutants
• 66.7% of mutants exhibit blepharoptosis and conjunctivitis with increasing age

integument
• mutants exhibit decreased temperature perception, with mutants staying on a hot plate at higher temperatures than controls
• however, the discomfort caused by temperature perception tests leads to an exaggerated nocifensive response in mutants, with mutants jumping high multiple times and this behavior persists after the noxious stimulus has ceased, unlike in controls, indicating that while mutants show decreased temperature perception, they show exaggerated responses once they feel the pain

Mouse Models of Human Disease
OMIM IDRef(s)
Neuropathy, Hereditary Sensory and Autonomic, Type III; HSAN3 223900 J:188923