About   Help   FAQ
Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Gucy2etm1Gar
targeted mutation 1, David L Garbers
MGI:2183212
Summary 4 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Gucy2etm1Gar/Gucy2etm1Gar involves: 129S6/SvEvTac MGI:3711277
hm2
Gucy2etm1Gar/Gucy2etm1Gar involves: 129S6/SvEvTac * C57BL/6 MGI:3693895
cx3
Gucy2etm1Gar/Gucy2etm1Gar
Nrltm1Asw/Nrltm1Asw
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 MGI:6110583
cx4
Gucy2etm1Gar/Gucy2etm1Gar
Gucy2ftm1Wbae/Gucy2ftm1Wbae
involves: 129S6/SvEvTac MGI:3711279


Genotype
MGI:3711277
hm1
Allelic
Composition
Gucy2etm1Gar/Gucy2etm1Gar
Genetic
Background
involves: 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gucy2etm1Gar mutation (1 available); any Gucy2e mutation (30 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Ultrastructure of wild type and degenerative Gucy2etm1Gar/Gucy2etm1Gar cone outer segments

vision/eye
• at distal connecting cilia, membrane components are partitioned into layered stacks
• apical inner segments of cones appear retracted from connecting cilia and surrounded by extracellular blebs
• at 2 months of age, cone outer segments (COS) in retinas are extremely disorganized
• in severely degenerated cases, membranes are detached
• sensitivity of rods to light (half-saturating flash intensity of 13.6 photons/um2) is 3.5-fold higher than wild-type
• scotopic a- and b-wave amplitudes in 4-6 week old mice are significantly reduced compared to wild-type responses
• after exposure to high intensity light, followed by 1 hour of dark adaptation, a-wave amplitude recovery is delayed relative to wild-type, with only 30% recovery

nervous system
• at distal connecting cilia, membrane components are partitioned into layered stacks
• apical inner segments of cones appear retracted from connecting cilia and surrounded by extracellular blebs
• at 2 months of age, cone outer segments (COS) in retinas are extremely disorganized




Genotype
MGI:3693895
hm2
Allelic
Composition
Gucy2etm1Gar/Gucy2etm1Gar
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gucy2etm1Gar mutation (1 available); any Gucy2e mutation (30 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• by 5 weeks of age, number of identifiable cones is dramatically reduced
• cells degenerate rapidly at 4-5 weeks of age, with few surviving at late stages
• by 1 month of age, electroretinograms (ERG) of mutant mice are abnormal
• at one month of age, cone responses to flashes in rod-saturating background are barely detectable
• rod a-wave and b-wave of ERG are severely reduced at one month of age
• flash response from a rod demonstrates increased time-to-peak before decaying more rapidly than in controls; rods have a higher sensitivity than wild-type
• rods show oscillations during and after recovery from a light flash

nervous system
• by 5 weeks of age, number of identifiable cones is dramatically reduced
• cells degenerate rapidly at 4-5 weeks of age, with few surviving at late stages

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
cone-rod dystrophy 6 DOID:0111011 OMIM:601777
J:77627




Genotype
MGI:6110583
cx3
Allelic
Composition
Gucy2etm1Gar/Gucy2etm1Gar
Nrltm1Asw/Nrltm1Asw
Genetic
Background
involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gucy2etm1Gar mutation (1 available); any Gucy2e mutation (30 available)
Nrltm1Asw mutation (1 available); any Nrl mutation (13 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
vision/eye
• 6 month old mice have fewer cones in the inferior versus superior retinas
• outer nuclear layer (ONL) is 28% thinner than in single Nrl homozygotes at 6 months of age
• treatment with an adenovirus expressing Gucy2e results in cone preservation with increased ONL thickness
• ERG indicates no discernible wave forms, with no M-cone or S-cone responses
• subretinal injection of an adenovirus expressing Gucy2e at around P41, but not at P18, fully restores retinal function and useful vision over the long-term
• mice treated with an adenovirus expressing human GUCY2D at P40 exhibit restored retinal function

behavior/neurological
• visually guided behavior testing (optokinetic reflex) shows decreased cone-mediated spatial frequency thresholds at 6 months of age

homeostasis/metabolism
• no retinal guanylate cyclase activity in the retina

nervous system
• 6 month old mice have fewer cones in the inferior versus superior retinas

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Leber congenital amaurosis 1 DOID:0110078 OMIM:204000
J:241970




Genotype
MGI:3711279
cx4
Allelic
Composition
Gucy2etm1Gar/Gucy2etm1Gar
Gucy2ftm1Wbae/Gucy2ftm1Wbae
Genetic
Background
involves: 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gucy2etm1Gar mutation (1 available); any Gucy2e mutation (30 available)
Gucy2ftm1Wbae mutation (0 available); any Gucy2f mutation (5 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

Abnormal rod outer segments in Gucy2etm1Gar/Gucy2etm1Gar Gucy2ftm1Wbae/Gucy2ftm1Wbae mice

vision/eye
• retinas have slightly decreased cone numbers relative to controls
• at 2 months of age, outer segment lengths are ~50-70% of normal
• cone cell remnants are identified in the retina, but outer segments are absent
• cone degeneration is most severe inferior to the optic nerve
• complete lack of cGMP
• rods are surrounded by blebs in interphotoreceptor matrix
• at 6 months of age, rod outer segments are severely reduced in superior/inferior and nasal/temporal quadrants
• in retina, rod outer segments are shorter and narrower than in wild-type, and appear banded by alternating regions of dense membrane layers and lumen-containing tubules
• at 6 months of age, outer nuclear layer (ONL) contains only 4-6 rows of nuclei
• scotopic electroretinographic responses are absent in all double homozygotes
• no detectable light-sensitive current is detectable in rods
• after exposure to high intensity light, followed by 1 hour of dark adaptation, a-wave amplitude recovery is completely absent in mutants compared to 70% recovery in wild-type

nervous system
• retinas have slightly decreased cone numbers relative to controls
• at 2 months of age, outer segment lengths are ~50-70% of normal
• cone cell remnants are identified in the retina, but outer segments are absent
• cone degeneration is most severe inferior to the optic nerve
• complete lack of cGMP
• rods are surrounded by blebs in interphotoreceptor matrix
• at 6 months of age, rod outer segments are severely reduced in superior/inferior and nasal/temporal quadrants
• in retina, rod outer segments are shorter and narrower than in wild-type, and appear banded by alternating regions of dense membrane layers and lumen-containing tubules

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Leber congenital amaurosis 1 DOID:0110078 OMIM:204000
J:120903





Contributing Projects:
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 & Copyright Notice
Send questions and comments to User Support.
last database update
06/23/2022
MGI 6.20
The Jackson Laboratory