Phenotypes associated with this allele

• Allele Symbol: Gnpat^tm1Just
• Allele Name: targeted mutation 1, Wilhelm W Just
• Allele ID: MGI:2670461
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gnpat^tm1Just/Gnpat^tm1Just	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:2670462
hm2	Gnpat^tm1Just/Gnpat^tm1Just	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1	MGI:6423170

Genotype
MGI:2670462

hm1

• Allelic Composition: Gnpat^tm1Just/Gnpat^tm1Just
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

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

mortality/aging

premature death ( J:84690 )

• 40% died within the first 4 to 6 weeks of life

• some mice survived through 18 months of age, in most cases the long-lived mice were females

pigmentation

abnormal retina pigment epithelium morphology ( J:84690 )

endocrine/exocrine glands

small ovary ( J:84690 )

♀ • ovaries were reduced in size, however both folliculogenesis and ovulation occurred normally

abnormal seminiferous tubule morphology ( J:84690 )

♂ • diameter decreased by 40%

♂ • disorganization of the seminiferous epithelium

♂ • increased number of apoptotic cells in the seminiferous tubules relative to wild-type

growth/size/body

decreased body weight ( J:84690 )

• mice were 30% to 40% underweight relative to controls during the first 2 weeks of life

disproportionate dwarf ( J:84690 )

postnatal growth retardation ( J:84690 )

homeostasis/metabolism

abnormal lipid homeostasis ( J:84690 )

• absence of plasmalogens

• reduced brain levels of docosahexaenoic acid (DHA)

limbs/digits/tail

short limbs ( J:84690 )

• not as conspicuous as in humans with RCDP

reproductive system

azoospermia ( J:84690 )

♂ • the epididymides were devoid of sperm

small ovary ( J:84690 )

♀ • ovaries were reduced in size, however both folliculogenesis and ovulation occurred normally

abnormal seminiferous tubule morphology ( J:84690 )

♂ • diameter decreased by 40%

♂ • disorganization of the seminiferous epithelium

♂ • increased number of apoptotic cells in the seminiferous tubules relative to wild-type

arrest of male meiosis ( J:84690 )

♂ • partial arrest occurring between pachytene primary spermatocytes and the stage of round spermatids

male infertility ( J:84690 )

♂

vision/eye

optic nerve hypoplasia ( J:84690 )

abnormal retina pigment epithelium morphology ( J:84690 )

abnormal eye anterior chamber morphology ( J:84690 )

• dysgenesis of the anterior eye chamber

cataract ( J:84690 )

lenticonus ( J:84690 )

• anterior lenticonus

persistence of hyaloid vascular system ( J:84690 )

microphthalmia ( J:84690 )

• 20% reduction in eye diameter

nervous system

abnormal cerebellar granule cell migration ( J:148119 )

• at P20, granule cell precursors (GCP) are present in the external granule layer, which were absent in age-matched controls, indicating a delay in GCP migration

abnormal cerebellar foliation ( J:148119 )

• at P10 to P45, the intraculminate, declival and uvular fissures are poorly developed or missing in the mutant cerebellum and lobe IV/V is elongated and folia VI/VII appear to be particularly affected; at P20, reduced depth of the intracrural fissure is also seen

decreased brain weight ( J:148119 )

abnormal cerebral hemisphere morphology ( J:148119 )

• reduced size of cerebral hemispheres

abnormal Purkinje cell morphology ( J:148119 )

• Purkinje cells of adult mutant mice revealed a hyperspiny phenotype distinguished by additional perisomatic dendrites and multiple perisomatic and proximal dendritic spines not observed in age-matched controls

small cerebellum ( J:148119 )

• reduced size of cerebellum hemispheres

abnormal paranode morphology ( J:148119 )

• the length of the paranodes was significantly extended in the mutants

• dispersion of the Caspr signal was most pronounced in the optic nerve, but also significant in the corpus callosum and the cerebellum

abnormal paranodal axoglial junction morphology ( J:148119 )

• Purkinje cell axons, particularly those having large diameters, to be clearly altered missing the typical transverse bands either along the entire paranode or at individual loops

optic nerve hypoplasia ( J:84690 )

abnormal myelination ( J:148119 )

• by P20 myelination in the mutant vermis is considerably delayed especially in folia IV/V and VI, but the hypomyelination became less pronounced with advancing age

• by P45, the reduced myelination mutant mice is predominantly apparent in folium VI

• at P20, the initial non-myelinated portion of the axon was significantly extended in the optic nerve

decreased nerve conduction velocity ( J:148119 )

• a 40% decrease in nerve conduction velocity of callosal myelinated fibers is seen, but hippocampal Schaffer collaterals, which in rat and mouse are largely unmyelinated, do not alterations in nerve conduction

cellular

azoospermia ( J:84690 )

♂ • the epididymides were devoid of sperm

abnormal cerebellar granule cell migration ( J:148119 )

• at P20, granule cell precursors (GCP) are present in the external granule layer, which were absent in age-matched controls, indicating a delay in GCP migration

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rhizomelic chondrodysplasia punctata type 2		DOID:0110852	OMIM:222765	J:84690

Genotype
MGI:6423170

hm2

• Allelic Composition: Gnpat^tm1Just/Gnpat^tm1Just
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1

behavior/neurological

impaired contextual conditioning behavior ( J:286038 )

• mice exhibit reduced freezing responses in contextual fear conditioning

impaired cued conditioning behavior ( J:286038 )

• mice show reduced freezing responses in cued fear conditioning

increased coping response ( J:286038 )

• mice show reduced immobility in the forced swim test

• however, mice show no alteration in the tail suspension test, with mice spending a similar immobile time as wild-type mice

decreased anxiety-related response ( J:286038 )

• in the elevated plus maze, mice show increased counts of open arm entries without alternations in the time spent in the open arms indicating slightly reduced levels of anxiety

• in the light/dark box, mice show an increase in exploration distance in the light zone compared to wild-type mice, however, mice do not enter the light zone more often than wild-type mice, indicating slightly reduced levels of anxiety

• however, mice do not show differences in the novelty-suppressed feeding test, indicating no anxiety-related reduced behavior in response to a novel environment

decreased freezing behavior ( J:286038 )

• mice exhibit reduced freezing responses in the contextual and cued fear conditioning

hyperactivity ( J:286038 )

decreased stereotypic behavior ( J:286038 )

• mice do not at all engage in digging behavior, leaving most marbles in their place, although they interact with the marble by sniffing or trying to bite them

• mice exhibit normal nesting behavior, utilizing the nestlets similarly to wild-type mice, however they show reduced nestlet shredding

abnormal social investigation ( J:286038 )

• in the 3-chamber sociability test, mice show reduced sociability, with mice spending only slightly more time interacting with the stranger mouse than with the inanimate object

• however, mice show no apparent changes in the response to social novelty

taste/olfaction

taste/olfaction phenotype ( J:286038 )

N • mice exhibit normal olfaction in the buried food test

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
disease of mental health		DOID:150		J:286038