Analysis Tools|
Allele Symbol Allele Name Allele ID |
Rbl1tm1Tyj targeted mutation 1, Tyler Jacks MGI:1857448 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
17 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Background Sensitivity: on an inbred 129/Sv genetic background, homozygotes display no overt abnormalities up to 10 months of age; however, close examination reveals subtle thickening of the bones of the forelimbs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• homozygotes are viable, fertile, and display no developmental or pathological defects at 4-12 months of age
• neither tumors nor increased morbidity or mortality are observed up to 24 months of age
|
| N |
• mutant embryonic fibroblasts (passage 4-6) derived from 12.5-day-old homozygotes exhibit normal cell cycle characteristics relative to wild-type cells
|
| N |
• newborn homozygotes display normal epidermal terminal differentiation relative to heterozygous mutant littermates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• heterozygotes are viable and fertile; no increased morbidity or mortality is observed up to 24 months of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected with an adenovirus expressing cre-recombinase (AdCre) into the bladder lumen all develop bladder lesions that resemble high-grade non-muscle-invasive carcinoma
• bladder tumors display high proliferation and invade the basal lamina
• metastases are not seen for up to 1 year after AdCre infection
|
|
• hematuria is sometimes seen in mice injected with AdCre into the bladder lumen with bladder lesions
|
|
• mice injected with an adenovirus expressing cre-recombinase (AdCre) into the bladder lumen all develop bladder lesions that resemble high-grade non-muscle-invasive carcinoma
• bladder tumors display high proliferation and invade the basal lamina
• metastases are not seen for up to 1 year after AdCre infection
|
|
• hematuria is sometimes seen in mice injected with AdCre into the bladder lumen with bladder lesions
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| urinary bladder cancer | DOID:11054 |
OMIM:109800 |
J:217195 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites
• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber
|
|
• tumor cells that invade the anterior eye chamber beneath the cornea are densely packed stage II cells surrounded by sparse regions of plexus with no synaptic densities or vesiclesin in the plexus or rosettes of these cells
• tumor cells have abundant mitochondria and mitotic figures; some rosettes have a central plexus made up of large, undifferentiated processes, with other rosettes having a central plexus containing neurons and synapses
|
|
• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in extensive plexus areas of tumors
|
|
• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites
• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber
|
|
• a substantial proportion of tumor cells expressing amacrine/horizontal cell markers are proliferating as shown by labeled thymidine incorporation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tumor cells that invade the anterior eye chamber beneath the cornea are densely packed stage II cells surrounded by sparse regions of plexus with no synaptic densities or vesiclesin in the plexus or rosettes of these cells
• tumor cells have abundant mitochondria and mitotic figures; some rosettes have a central plexus made up of large, undifferentiated processes, with other rosettes having a central plexus containing neurons and synapses
|
|
• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in smaller areas of plexus in tumors
• processes are usually smaller in diameter (<0.5 um) but large ones of 1-3 um are observed occasionally; variety of synaptic arrangements occur and all types can be found in contacts among processes, while ribbon synapses are seen only in areas near photoreceptor cell bodies
|
|
• significant disruptions in retinal morphology are observed by P12 to 13
• in diseased eyes, retina blastoma cells rupture the inner limiting membrane (ILM), particularly by the apex of vitreal protrusions that may be present; at these points, tumor cell bodies and associated vasculature can be seen
|
|
• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants; tumor size varies with age and genotype
• an early-stage tumor displayed a pronounced vitreal protrusion in one animal, and contained structures resembling neuronal processes like those in the plexiform layer of the normal retina
• in tumors, proteins usually found in amacrine/horizontal cells, including Gad65, Snap25, Calbindin, vGlut-1, E-cadherin, N-cadherin, synapsin, and Syntaxin-1 are expressed; these cells are considered to be differentiated
• cells positive for amacrine/horizontal cell markers (1.7-3.6 x 106 cells/tumor) are much more numerous than number of amacrine/horizontal cells in a normal retina
• regions of tumors negative for amacrine/horizontal markers contain more densely packed nuclei
|
|
• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants; tumor size varies with age and genotype
• an early-stage tumor displayed a pronounced vitreal protrusion in one animal, and contained structures resembling neuronal processes like those in the plexiform layer of the normal retina
• in tumors, proteins usually found in amacrine/horizontal cells, including Gad65, Snap25, Calbindin, vGlut-1, E-cadherin, N-cadherin, synapsin, and Syntaxin-1 are expressed; these cells are considered to be differentiated
• cells positive for amacrine/horizontal cell markers (1.7-3.6 x 106 cells/tumor) are much more numerous than number of amacrine/horizontal cells in a normal retina
• regions of tumors negative for amacrine/horizontal markers contain more densely packed nuclei
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice have much more aggressive, invasive form of retinoblastoma than Trp53-sufficient compound mutants, but onset is delayed compared to that observed in Rbl1 homozygous compound mutants
• tumor size varies with age and genotype
• mice show rapid filling of the vitreal cavity with densely packed tumor cells and rosettes; in the tumors, there is an overabundance of stage II retinoblastoma cells
• near outer surface of retina near tumor origin site, there are regions of plexus with synaptic densities and synaptic vesicles, indistinguishable from the Rb1;Rbl1 mutants that are wild-type for Trp53
|
|
• significant disruptions in retinal morphology are observed by P12 to 13
|
|
• significant disruptions in retinal morphology are observed by P12 to 13
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice with retinoblastoma tumors are characterized by pronounced loss of photoreceptor cells
|
|
• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites
• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber
• tumors show appearance of unique populations of undifferentiated tumor-like cells, and extensive formation of plexiform regions
• in a large tumor that filled much of the vitreal space contained two cell types: some cells are stage I retinoblastoma cells with pale, round nuclei resembling differentiated neurons and always associated with a plexus or tightly-packed stage II retinoblastoma cells with irregular nuclei with little or no plexus associated with individual cells
• rosettes in retinoblastomas are usually composed of stage I cells with a central plexus, but are adjacent to clusters of stage II cells
• plexus regions of tumors show mitotic figures and apoptotic cells; plexus regions also contained synaptic densities and associated synaptic vesicles
|
|
• areas of the plexus within the posterior chamber are composed of neuron-like processes having synaptic structures similar to horizontal/amacrine cells; this is seen in smaller areas of plexus in tumors
• processes are usually smaller in diameter (<0.5 um) but large ones of 1-3 um are observed occasionally; variety of synaptic arrangements occur and all types can be found in contacts among processes, while ribbon synapses are seen only in areas near photoreceptor cell bodies
|
|
• significant disruptions in retinal morphology are observed by P12 to 13
|
|
• retinoblastoma cells that express amacrine/horizontal cell markers also extend processes and form synapses; some of these Golgi-Cox-labeled cells extend 1-3 long main processes with further neurite branching characteristic of horizontal or wide-field amacrine cells, while more (nearly half of ) labeled cells extend a main process with extensive neurite outgrowth characteristic of amacrine cells, and the remaining cells are less differentiated with short, unbranched neurites
• these labeled cells are mainly found near the tumor origin, while fewer are present toward the lens and anterior chamber
• tumors show appearance of unique populations of undifferentiated tumor-like cells, and extensive formation of plexiform regions
• in a large tumor that filled much of the vitreal space contained two cell types: some cells are stage I retinoblastoma cells with pale, round nuclei resembling differentiated neurons and always associated with a plexus or tightly-packed stage II retinoblastoma cells with irregular nuclei with little or no plexus associated with individual cells
• rosettes in retinoblastomas are usually composed of stage I cells with a central plexus, but are adjacent to clusters of stage II cells
• plexus regions of tumors show mitotic figures and apoptotic cells; plexus regions also contained synaptic densities and associated synaptic vesicles
|
|
• mice with retinoblastoma tumors are characterized by pronounced loss of photoreceptor cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in 61% of mice visible unilateral retinoblastoma develop with delayed and variable kinetics appearing on average by 208 +/- 17 days relative to mice lacking Rbl2
• unlike mice lacking Rbl2, bilateral visible retinoblastomas are rare
• however, 3 of 11 retinas from mice with unilateral tumors in the opposite eye contain early retinoblastomas with mitotic figures and Homer-Wright rosettes
• at P60 4 of 14 eyes have retinoblastomas at level of the optic nerve head in the extreme periphery of the retina
|
|
• in 11 of 11 mice with unilateral tumors, the retina in the tumor free eye is disorganized and degenerated
• at P31 6 of 24 retinas have dysplastic lesions containing Homer-Wright rosettes at the level of the optic nerve in the extreme periphery and increased proliferation in the periphery without histological evidence of retinoblastoma
|
|
• in 61% of mice visible unilateral retinoblastoma develop with delayed and variable kinetics appearing on average by 208 +/- 17 days relative to mice lacking Rbl2
• unlike mice lacking Rbl2, bilateral visible retinoblastomas are rare
• however, 3 of 11 retinas from mice with unilateral tumors in the opposite eye contain early retinoblastomas with mitotic figures and Homer-Wright rosettes
• at P60 4 of 14 eyes have retinoblastomas at level of the optic nerve head in the extreme periphery of the retina
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| retinoblastoma | DOID:768 |
OMIM:180200 |
J:119919 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice injected intrasplenicaly with adenovirus expressing Cre recombinase develop multiple liver lesions after a latency of 3-4 months
• tumors resemble human hepatocellular carcinoma
• expansion of populations of stem/progenitor cells suggests that these cells, not hepatocytes, are the initiating populations in hepatocellular carcinoma development
• mutants treated with DAPT, a gamma-secretase inhibitor, 75 days after adenoviral Cre injection, show macroscopically visible tumors 12 days after the beginning of treatment
|
|
• mice injected intrasplenicaly with adenovirus expressing Cre recombinase develop multiple liver lesions after a latency of 3-4 months
• tumors resemble human hepatocellular carcinoma
• expansion of populations of stem/progenitor cells suggests that these cells, not hepatocytes, are the initiating populations in hepatocellular carcinoma development
• mutants treated with DAPT, a gamma-secretase inhibitor, 75 days after adenoviral Cre injection, show macroscopically visible tumors 12 days after the beginning of treatment
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| hepatocellular carcinoma | DOID:684 |
OMIM:114550 |
J:177573 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice with mosaic cre expression due to maternal inheritance of Tg(Nes-cre)1Mrt die prior to weaning
|
|
• mice exhibit higher apoptosis levels than in wild-type and Rb1tm3Tyj/Rb1tm3Tyj Tg(Nes-cre)1Mrt mice
|
|
• at E18.5, massive retinal dysplasia is evident
|
|
• mice exhibit higher apoptosis levels than in wild-type and Rb1tm3Tyj/Rb1tm3Tyj Tg(Nes-cre)1Mrt mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• these mutant mice exhibit only a subtle and transient growth retardation from which they recover at 3 weeks of age
|
| N |
• at 16.0-19.0 dpc, these mutant embryos display normal forelimb development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• generally, double mutants are born alive but die shortly after birth
|
|
• occasionally, double mutant mice are not removed from their amniotic sacs by their mothers and either are born dead or die partly as a result of maternal rejection
|
|
• at 19.0 dpc, the interparietal bone of double mutant mice appears underdeveloped; most other cranial bones develop normally
|
|
• at 19.0 dpc, the supraoccipital bone of double mutant mice appears slightly underdeveloped
|
|
• a few double mutant embryos display incisors anodontia with undifferentiated mesenchymal tissue
|
|
• most double mutant embryos exhibit incisors microdontia
|
|
• when present, the tooth germ of double mutant embryos shows variable degrees of microdontia along with hypoplasia and disorganization of the odontoblast layer
|
|
• at 16.0 dpc, the mutant humerus shows complete lack of ossification
|
|
• at 19.0 dpc, double mutants show abnormal thickening of the humerus
|
|
• at 19.0 dpc, double mutants show abnormal shortening of the humerus
|
|
• at 19.0 dpc, double mutants show abnormal shortening of the radius
|
|
• at 19.0 dpc, double mutants show abnormal thickening of the radius
|
|
• at 19.0 dpc, double mutants show abnormal shortening of the ulna
|
|
• at 19.0 dpc, double mutants show abnormal thickening of the ulna
|
|
• at 18.0 dpc, some double mutants display abnormal tracheal cartilage formation, contributing to airway dysfunction and possibly neonatal lethality
|
|
• at 18 dpc, the growth plates of mutant humerus appear widened, the epiphyses are deformed and thickened, and the zone of flattened cells elongated
|
|
• chondrocytes in the epiphyseal centers of mutant humeri proliferate at an increased rate and reach and higher density
• chondrocytes in the zone of flattened cells exhibit a delay in the cell cycle withdrawal and hypertrophy associated with terminal differentiation
• however, chondrocytes eventually stop proliferating in mutant growth plates
|
|
• in 18.0 dpc mutant humerus, hypertrophic chondrocytes fail to form well-organized columns, and ossification of cancellous bone begins at an increased distance from the articular surface
|
|
• abnormal rib development may prevent adequate lung expansion and inflation, contributing to neonatal lethality
|
|
• at 16.0 dpc, double mutants show a reduced rib cage size
|
|
• at 18.0 dpc, chondrocyte density in the epiphyseal centers of mutant humeri is increased by ~2-fold; at 16.5 dpc, chondrocyte density is increased by ~30%
|
|
• at 16.0 dpc, double mutants display reduced ossification of the long bones of the fore- and hindlimbs, including complete loss of ossification in the humerus
|
|
• at 19.0 dpc, the interparietal bone of double mutant mice appears underdeveloped; most other cranial bones develop normally
|
|
• at 19.0 dpc, the supraoccipital bone of double mutant mice appears slightly underdeveloped
|
|
• a few double mutant embryos display incisors anodontia with undifferentiated mesenchymal tissue
|
|
• most double mutant embryos exhibit incisors microdontia
|
|
• when present, the tooth germ of double mutant embryos shows variable degrees of microdontia along with hypoplasia and disorganization of the odontoblast layer
|
|
• beginning at 15.0-16.0 dpc, double mutants display a shortened snout
|
|
• at 16.0 dpc, the mutant humerus shows complete lack of ossification
|
|
• at 19.0 dpc, double mutants show abnormal thickening of the humerus
|
|
• at 19.0 dpc, double mutants show abnormal shortening of the humerus
|
|
• at 19.0 dpc, double mutants show abnormal shortening of the radius
|
|
• at 19.0 dpc, double mutants show abnormal thickening of the radius
|
|
• at 19.0 dpc, double mutants show abnormal shortening of the ulna
|
|
• at 19.0 dpc, double mutants show abnormal thickening of the ulna
|
|
• beginning at 15.0-16.0 dpc, double mutants have significantly shorter limbs
|
|
• at 18.0 dpc, some double mutants display abnormal tracheal cartilage formation, contributing to airway dysfunction and possibly neonatal lethality
|
|
• prior to death, double mutant neonates exhibit breathing abnormalities and poor oxygenation
|
|
• in double mutant neonates, abnormal endocranial bone formation may result in compression of the cervical spinal canal and observed lethal apnea
|
|
• a few double mutant embryos display incisors anodontia with undifferentiated mesenchymal tissue
|
|
• most double mutant embryos exhibit incisors microdontia
|
|
• when present, the tooth germ of double mutant embryos shows variable degrees of microdontia along with hypoplasia and disorganization of the odontoblast layer
|
|
• beginning at 15.0-16.0 dpc, double mutants display a shortened snout
|
|
• at 18.5 dpc, double mutants are up to 30% smaller than littermates
|
|
• beginning at 15.0-16.0 dpc, double mutant embryos display a significant reduction in size
|
|
• beginning at 15.0-16.0 dpc, double mutants display a moderately distended abdomen
|
|
• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdcscid mice frequently display hyperplasic sebaceous glands
|
|
• newborn double homozygotes exhibit abnormal terminal differentiation of epidermal keratinocytes
• in addition, grafts of double mutant epidermis placed onto NOD Prkdcscid mice show aberrant keratinocyte differentiation and hyperproliferation in the basal cells of interfollicular epidermis; proliferating cells are also detected in some cells of the suprabasal layer
|
|
• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdcscid mice frequently display hyperplasic sebaceous glands
|
|
• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdcscid mice frequently exhibit multiple dysplastic hair follicles sharing a single hair channel as well as multiple follicular keratin-filled cysts
|
|
• newborn double homozygotes display a developmental delay in hair follicle formation that is associated with decreased Bmp4-dependent signaling in the epidermis
• this delay is first apparent at 14.5 dpc, concomitant with a severe reduction in the number of hair germs, and persists at 16.5 and 18.5 dpc, suggesting impaired morphogenesis and development of both tylotrich and nontylotrich hair follicles
• normal hair growth is restored when grafts of double mutant epidermis are placed onto NOD Prkdcscid mice: at 4 weeks after transplantation, mutant skin grafts show normal anagen hair follicles with normal epithelial layers and hair bulbs
• in spite of normal hair formation, mutant skin grafts display several defects in hair morphogenesis, development and cycling
|
|
• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdcscid mice frequently have twisted hair follicles lying in parallel to the epidermal surface
|
|
• newborn double homozygotes show a generalized reduction in the number of hair follicles
• notably, at 4 weeks after transplantation, grafts of double mutant epidermis placed onto NOD Prkdcscid mice display a 3-fold increase in the number of hair follicles
|
|
• at 14.5 dpc, double mutant embryos exhibit a developmental delay of whiskers
|
|
• at 8 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdcscid mice continue to display most hair follicles in anagen as opposed to the expected resting telogen phase
|
|
• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdcscid mice frequently display parakeratosis
|
|
• newborn double homozygotes show a decrease in the number and size of keratohyalin granules of the stratum granulosum
|
|
• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdcscid mice frequently display epidermal hyperplasia
|
|
• newborn double homozygotes exhibit abnormal terminal differentiation of epidermal keratinocytes
• in addition, grafts of double mutant epidermis placed onto NOD Prkdcscid mice show aberrant keratinocyte differentiation and hyperproliferation in the basal cells of interfollicular epidermis; proliferating cells are also detected in some cells of the suprabasal layer
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• similar to Rb1tm1Tyj heterozygotes, mice heterozygous for both Rb1tm1Tyj and Rbl1tm1Tyj die from tumors in the intermediate lobe of the pituitary gland at ~12 months of age
|
|
• double heterozygotes develop large pituitary tumors of the intermediate lobe that are comparable to those arising in single Rb1tm1Tyj heterozygotes with respect to both incidence and size
• such pituitary tumors are shown to arise from cells in which the wild-type allele of Rb1 is absent, whereas the wild-type allele of Rbl1 is retained
|
|
• double heterozygotes develop large pituitary tumors of the intermediate lobe that are comparable to those arising in single Rb1tm1Tyj heterozygotes with respect to both incidence and size
• such pituitary tumors are shown to arise from cells in which the wild-type allele of Rb1 is absent, whereas the wild-type allele of Rbl1 is retained
|
|
• double heterozygotes develop large pituitary tumors of the intermediate lobe that are comparable to those arising in single Rb1tm1Tyj heterozygotes with respect to both incidence and size
• such pituitary tumors are shown to arise from cells in which the wild-type allele of Rb1 is absent, whereas the wild-type allele of Rbl1 is retained
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E10.5, 2 out of 10 double mutants are found dead and 2 are noticeably smaller; also, 9 out of 19 double mutants die at E11.5, that is 2 days earlier than mice homozygous for Rb1tm1Tyj alone
• by E12.5, 7 out of 8 double mutant embryos are either dead or in various stages of resorption
|
|
• at E11.5, double mutant embryos exhibit a significantly high frequency of pyknotic nuclei (i.e. apoptosis) in the CNS; in contrast, single Rb1tm1Tyj homozygotes show extensive CNS apoptosis at later stage (E13.5)
• at E12.5 (but not E11.5), a viable double mutant (1 out of 8) exhibits abnormally high levels of apoptosis in the liver and CNS; in contrast, single Rb1tm1Tyj homozygotes show extensive liver apoptosis at later stage
|
|
• at E11.5, viable double mutant embryos exhibit disorganization of the endothelial linings of yolk sac vessels
|
|
• at E11.5 days, 2 out of 19 double mutant embryos are significantly smaller than control embryos
|
|
• at E11.5, viable double mutant embryos show a significant reduction of erythrocytes in the yolk sac blood vessels
|
|
• at E11.5 days, 2 out of 19 double mutant embryos are significantly smaller than control embryos
|
| N |
• at E12.5, double mutant embryos show normal myogenic commitment and differentiation
|
|
• at E11.5, viable double mutant embryos exhibit disorganization of the endothelial linings of yolk sac vessels
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• females displaying vaginal atresia accumulate fluid in the uterus and die between 4 and 6 months of age
|
|
• similar to Rb1tm1Tyj heterozygotes, any surviving mutant mice eventually die of pituitary tumors after 12 months
|
|
• at 1 week of age, mutant pups are obtained at a significantly lower frequency (19%) than expected (25%)
• most mutants die within the first 3 weeks of age, with only about 25% surviving beyond 3 weeks
|
|
• similar to Rb1tm1Tyj heterozygotes, all surviving mutant mice develop large pituitary adenocarcinomas of the intermediate lobe
|
|
• mutant pups become runted several days after birth
|
|
• beginning at ~1 week, mutant pups appear severely growth retarded, averaging 50% of the weight of control littermates
• mutants surviving beyond 3 weeks of age gain weight slowly, averaging 70-90% of normal weight at 3 months
|
|
• although mutant pups are of approximately uniform size at birth, a number of pups display severe growth retardation, with weight differences persisting for several weeks
|
|
• females displaying vaginal atresia have a distended abdomen as a result of fluid accumulation in the uterus
|
|
• similar to Rb1tm1Tyj heterozygotes, all surviving mutant mice develop large pituitary adenocarcinomas of the intermediate lobe
|
|
• females displaying vaginal atresia have a distended perineum as a result of fluid accumulation in the uterus
|
 |
• ~75% of mutant females display vaginal atresia whereas the majority of mutant males surviving beyond 3 weeks of age are fertile and appear normal up to 12 months
• in affected females, the vaginal opening is absent; however, the rest of the reproductive tract appears unaffected
|
|
• at 4-6 months, all mutant mice display retinal dysplasia; both eyes are affected in 11 out of 12 mutants
• typically, each eye contains 5-7 individual lesions composed of small white bodies (usually in clusters), indicating retinal pathology
|
|
• as early as 4 days after birth, mutant newborns exhibit mild, yet significant, disruptions of the retinal photoreceptor layer
|
|
• similar to Rb1tm1Tyj heterozygotes, all surviving mutant mice develop large pituitary adenocarcinomas of the intermediate lobe
|
|
• as early as 4 days after birth, mutant newborns exhibit mild, yet significant, disruptions of the retinal photoreceptor layer
|
|
• females displaying vaginal atresia have a distended perineum as a result of fluid accumulation in the uterus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die at an increased rate during the first and second week after birth; survivors fail to reach normal adult weight
|
|
• at 18.0 dpc, mutant mice exhibit forelimb shortening and thickening
|
|
• beginning at 15.0-16.0 dpc, mutants display a mild reduction in limb length
|
|
• at 18.0 dpc
|
|
• surviving mutant mice display delayed fertility
|
|
|
• surviving mutant females show reduced fertility
|
|
• beginning at 15.0-16.0 dpc, mutants display a mildly shortened snout
|
|
• beginning at 15.0-16.0 dpc, mutants display a mildly shortened snout
|
|
• mutant mice display normal weight at birth but reach only ~65% of normal weight at the age of 2-3 weeks
|
|
• beginning at 15.0-16.0 dpc, mutants display a slightly distended abdomen
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 11/12/2024 MGI 6.24 |
|
|
|
||
