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Allele Symbol Allele Name Allele ID |
Tg(Hsp70-1-cre)6Arge transgene insertion 6, Argiris Efstratiadis MGI:2389573 |
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| Summary |
5 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• die between 6 and 8 weeks
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• diabetic in one week
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• extremely elevated
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• trimming litter size at birth allows 20% of mutants to survive postnatally
• 15 of 28 (54%) of mutants survive past 18 months of age, and 7 of these live up to 22-24 months of age with minor health problems
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• approximately 95% die perinatally
• trimming litter size at birth allows 20% of mutants to survive postnatally
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• 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
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• mutants weigh 70-80% the weight of control littermates at P21
• mutants over 11 months of age also display low body weight
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• mutants over 11 months of age are short in length (about 85-90% the length of control littermates)
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• postnatal growth is compromised, with mutants 70-80% the weight of control littermates at P21
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• starting at mid-gestation, embryos have a reduced growth rate
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• poor sucking and uncoordinated swallow at birth
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• adult mutants exhibit self-inflicted wounds from frequent scratching
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• adult mutants exhibit excessive grooming
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• hindlimb clasping on tail suspension in mutants surviving to adulthood
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• mutants surviving to adulthood exhibit an abnormal postural behavior (sitting-up) not observed in controls, most likely to compensate for the kyphoscoliosis
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• 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
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• handling-induced seizures in mutants surviving to adulthood
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• startling noise induced seizures in mutants that survive to adulthood
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• 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
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• mutant pups exhibit bubbles of air in their intestines at P18 indicating intestinal dysfunction
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• placenta growth is impaired, averaging 75% the size of wild-type placenta in embryos from mid-gestation onwards
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• mutants over 11 months of age have very little fat content
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• 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
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• 40% of mutants exhibit blepharoptosis and conjunctivitis with increasing age
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• handling-induced seizures in mutants surviving to adulthood
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• startling noise induced seizures in mutants that survive to adulthood
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• muscle spindles appear to develop normally but exhibit significantly reduced primary sensory afferent innervation
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• decrease in volume of sympathetic ganglia at birth (70% of controls)
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• at E18.5, fetuses show a significant reduction in the volume of stellate ganglia compared to controls
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• at E18.5, fetuses show a significant reduction in the volume of superior cervical sympathetic ganglia (SCG) compared to controls
• at P21, total volume of SCG is about 80% the volume of controls and neuronal cells are less densely packed
• by 10 months of age, both volume and neuronal density of sCGs are significantly reduced, with the volume of SCG being as low as 30% of controls
• however, localization and differentiation of sympathetic neurons in superior cervical, stellate, and celiac ganglia are normal
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• muscle spindles exhibit significantly reduced primary sensory afferent innervation
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• decrease in the convergence of retinal ganglion cells to the optic nerve in 22 month old mutants
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• urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 2 out of 3 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some
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• the optic nerve head is excavated in 22 month old mutants
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• the optic nerve head is excavated in 22 month old mutants and the retinal ganglion cell layer appears thinner
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• decrease in volume of the dorsal root ganglion (70% of controls)
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• mutants exhibit a small but significant decrease in the relative proportion of small dark B cells in lumbar dorsal root ganglia at 18 months of age
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• with increasing age, mutants exhibit phenotypes related to dysautonomia
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• urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 2 out of 3 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some
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• urine retention/neurogenic bladder and/or hydronephrosis is seen in 2 out of 3 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some
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• urine retention/neurogenic bladder (bladder distension) and/or hydronephrosis is seen in 2 out of 3 adult males starting at 11 months of age, with partial or complete destruction of one of the kidneys in some
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• 75% of mutants surviving to adulthood develop skeletal abnormalities, mostly kyphosis or kyphoscoliosis that worsens over time
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• 40% of mutants exhibit blepharoptosis and conjunctivitis with increasing age
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• decrease in the convergence of retinal ganglion cells to the optic nerve in 22 month old mutants
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• the optic nerve head is excavated in 22 month old mutants
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• the optic nerve head is excavated in 22 month old mutants and the retinal ganglion cell layer appears thinner
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• 40% of mutants exhibit blepharoptosis and conjunctivitis with increasing age
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• seen in 22 month old mutants
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• muscle spindles appear to develop normally but exhibit significantly reduced primary sensory afferent innervation
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Riley-Day syndrome | DOID:11589 |
OMIM:223900 |
J:188923 | |
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
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• 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
|
|
• 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
|
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• majority of pups are born with about 70% the weight and size of their control littermates
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• majority of pups are born with about 70% the weight and size of their control littermates
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• at P18-P21, mutants are approximately 32% the weight of wild-type littermates
• mutants over 11 months of age display low body weight
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• mutants over 11 months of age are short in length (about 85-90% the length of control littermates)
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• starting at mid-gestation, embryos have a reduced growth rate
|
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• newborn pups lack milk in stomachs
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• 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
|
|
• 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
|
|
• 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
|
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• mutant pups exhibit bubbles of air in their intestines at P13 indicating intestinal dysfunction
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• spongiotrophoblast layer is poorly developed at late gestation
• however the labyrinthine zone appears normal
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• placenta is small and thin at E16.5
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• placenta growth is impaired, averaging 55% the size of wild-type placenta in embryos from mid-gestation onwards
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• 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
|
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• 66.7% of mutants exhibit blepharoptosis and conjunctivitis with increasing age
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• mutants exhibit puffy feet at P18
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• 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
|
|
• 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
|
|
|
• 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
|
|
|
• 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
|
|
|
• 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
|
|
• 100% of mutants surviving to adulthood develop skeletal abnormalities, mostly kyphosis or kyphoscoliosis that worsens over time
|
|
• 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
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Riley-Day syndrome | DOID:11589 |
OMIM:223900 |
J:188923 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E11 at the spinal level the neural tube is smaller than normal
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• at E11, the neural tube is open at the midbrain and hindbrain levels but closed at the spinal level
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• forebrain structures are reduced in size
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• midbrain structures are reduced in size
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• specific classes of dorsal sensory interneurons, including D1A, D1B, and D2 neurons, are absent and the domain of generation of D3 neurons is shifted dorsally; however numbers of motor neurons and ventral interneurons are normal or slightly increased
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• at E11 at the spinal level the neural tube is smaller than normal
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• at E11, the neural tube is open at the midbrain and hindbrain levels but closed at the spinal level
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|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mammary tumors are observed in 7/12 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice
• in cell lines developed from individual mammary tumors from two of the conditional knockout mouse lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line
• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line
• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases
• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay
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|
• mammary tumors are observed in 7/12 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice
• in cell lines developed from individual mammary tumors from two of the conditional knockout mouse lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line
• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line
• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases
• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay
|
|
• mammary tumors are observed in 7/12 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice
• in cell lines developed from individual mammary tumors from two of the conditional knockout mouse lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line
• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line
• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases
• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Bloom syndrome | DOID:2717 |
OMIM:210900 |
J:112115 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/23/2024 MGI 6.23 |
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