Phenotypes associated with this allele

• Allele Symbol: Arl2bp^em1Visu
• Allele Name: endonuclease-mediated mutation 1, Visvanathan Ramamurthy
• Allele ID: MGI:6376642
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Arl2bp^em1Visu/Arl2bp^em1Visu	involves: 129S2/SvPasCrl * C57BL/6J * FVB/N	MGI:6376646
hm2	Arl2bp^em1Visu/Arl2bp^em1Visu	involves: FVB/N	MGI:6377057

Genotype
MGI:6376646

hm1

• Allelic Composition: Arl2bp^em1Visu/Arl2bp^em1Visu
• Genetic Background: involves: 129S2/SvPasCrl * C57BL/6J * FVB/N

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

vision/eye

abnormal retina photoreceptor morphology ( J:280811 )

• mice exhibit shortened photoreceptor axonemes at P16

• distal regions of photoreceptor axonemes show a reduced number of singlet structures and the 9 + 0 arrangement of microtubular structures is not seen

abnormal photoreceptor connecting cilium morphology ( J:280811 )

• photoreceptor connecting cilium show abnormal doublet microtubules organization, with multiple microtubules possessing open B-tubules which are not seen in wild-type indicating defective inner junction B-tubule closure

abnormal photoreceptor outer segment morphology ( J:280811 )

• mice show distorted and ragged outer segments at P16

• mice show dysmorphic outer segments, which includes misoriented and irregular disks of variable diameters, fragmented outer segments, and membranous whorls at P17

abnormal photoreceptor outer segment disc membrane morphology ( J:280811 )

• outer segments show misoriented and irregular discs of variable diameters, with most discs aligned vertically rather than horizontally

disorganized photoreceptor outer segment ( J:280811 )

retina photoreceptor degeneration ( J:280811 )

• photoreceptor cell death is seen at P16 with significant degeneration by P210

• however, retinal lamination appears normal at P16 and development of inner neurons is normal, with no alteration in bipolar or horizontal cell numbers

retina cone cell degeneration ( J:280811 )

• progressive loss of cones

decreased a-wave amplitude ( J:280811 )

• mice show a 67% decrease in rod-driven (scotopic) ERG response (a wave) at P16, when mice are just opening their eyes with progressive loss of function with a 90% reduction in rod photoresponse by P210

• mice show a decrease in cone-driven (photopic) ERG response (a wave) at P16 that progressively declines with age

nervous system

abnormal retina photoreceptor morphology ( J:280811 )

• mice exhibit shortened photoreceptor axonemes at P16

• distal regions of photoreceptor axonemes show a reduced number of singlet structures and the 9 + 0 arrangement of microtubular structures is not seen

abnormal photoreceptor connecting cilium morphology ( J:280811 )

• photoreceptor connecting cilium show abnormal doublet microtubules organization, with multiple microtubules possessing open B-tubules which are not seen in wild-type indicating defective inner junction B-tubule closure

abnormal photoreceptor outer segment morphology ( J:280811 )

• mice show distorted and ragged outer segments at P16

• mice show dysmorphic outer segments, which includes misoriented and irregular disks of variable diameters, fragmented outer segments, and membranous whorls at P17

abnormal photoreceptor outer segment disc membrane morphology ( J:280811 )

• outer segments show misoriented and irregular discs of variable diameters, with most discs aligned vertically rather than horizontally

disorganized photoreceptor outer segment ( J:280811 )

retina photoreceptor degeneration ( J:280811 )

• photoreceptor cell death is seen at P16 with significant degeneration by P210

• however, retinal lamination appears normal at P16 and development of inner neurons is normal, with no alteration in bipolar or horizontal cell numbers

retina cone cell degeneration ( J:280811 )

• progressive loss of cones

cellular

abnormal photoreceptor connecting cilium morphology ( J:280811 )

• photoreceptor connecting cilium show abnormal doublet microtubules organization, with multiple microtubules possessing open B-tubules which are not seen in wild-type indicating defective inner junction B-tubule closure

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
retinitis pigmentosa with or without situs inversus		DOID:0110419	OMIM:615434	J:280811

Genotype
MGI:6377057

hm2

• Allelic Composition: Arl2bp^em1Visu/Arl2bp^em1Visu
• Genetic Background: involves: FVB/N

mortality/aging

embryonic lethality, incomplete penetrance ( J:279003 )

• partial embryonic lethality at or near the time of gastrulation, between E7.5 and E13.5

growth/size/body

heterotaxia ( J:279003 )

• 28% of mice exhibit heterotaxy of either the heart or stomach

situs inversus ( J:279003 )

• 55% of mice exhibit situs inverus

nervous system

enlarged lateral ventricles ( J:279003 )

• 4-fold increase in lateral ventricular volume is seen in the brain

• however, mice do not present external signs of hydrocephaly

enlarged third ventricle ( J:279003 )

• the third ventricle appears enlarged

reproductive system

oligozoospermia ( J:279003 )

♂ • decrease in epididymal sperm cell count

teratozoospermia ( J:279003 )

♂ • sperm exhibit gross morphological defects, including numerous detached heads and tails, kinked necks, bent tails, stubby tails, abnormal heads, and cytoplasmic bulges attached to the tails

abnormal sperm flagellum morphology ( J:279003 )

♂ • males exhibit impaired sperm tail development, starting with the assembly of the core microtubular structure within the tail

♂ • sperm exhibit cytoplasmic bulges attached to the tails

abnormal sperm axoneme morphology ( J:279003 )

♂ • sperm tail axonemes are shortened and there is a decrease in axoneme-associated protein localization to the sperm tail, indicating impaired maturation of the axoneme

♂ • microtubules in sperm tails are present in parallel arrays in the proximal tail region but they do not form the canonical 9 + 2 axoneme arrangement; microtubules are singlets and are not paired and some seem to be incomplete tubules

abnormal sperm midpiece morphology ( J:279003 )

♂ • impaired midpiece formation, with poorly assembled outer dense fibers

abnormal sperm mitochondrial sheath morphology ( J:279003 )

♂ • the mitochondrial sheath contains centrally located mitochondria, but they are not properly organized

abnormal sperm fibrous sheath morphology ( J:279003 )

♂ • the fibrous sheath are not properly organized and are scattered in various portions of the tail indicating a failure to assemble properly

coiled sperm flagellum ( J:279003 )

♂ • sperm tails are spiraled

detached sperm flagellum ( J:279003 )

♂ • sperm exhibit numerous detached heads and tails

short sperm flagellum ( J:279003 )

♂

abnormal sperm head morphology ( J:279003 )

♂ • some sperm exhibit abnormal heads

abnormal acrosome morphology ( J:279003 )

♂ • sperm shows acrosomal irregularities with clusters of acrosomal granules instead of the cap structure, and at later stages in spermatogenesis, there are instances of irregularly shaped acrosomes surrounding nuclei

♂ • acrosome caps in testes at stages VIII-XI are irregularly shaped instead of round, with a delicate appearance and at stage XII, there are few misshapen acrosomes displaying a molar tooth shape

♂ • -however, most acrosomes on elongating spermatids appear normal

abnormal spermatid morphology ( J:279003 )

♂ • spermatids at stage IX display manchette and while the basal plate and capitulum are present in the neck, segmented columns are either absent or severely disrupted

immotile sperm ( J:279003 )

♂

abnormal spermiogenesis ( J:279003 )

♂ • marker analysis indicates a failure to complete spermiogenesis by the inability to form the outer dense fiber layer or assembly of the fibrous sheath and failure of sperm tail elongation

♂ • however, spermatogenesis appears to be normal through early tail formation, including formation of the manchette with centrally located centrioles

abnormal spermiation ( J:279003 )

♂ • sperm release into the lumen is impaired, with a smaller lumen area, an absence of sperm tails, and an increase in residual bodies

male infertility ( J:279003 )

♂

cellular

abnormal primary cilium morphology ( J:279003 )

• MEFs show shorter cilia after induction of primary cilia formation

• after 2 hours of serum addition, but not after 6-24 hours, a higher percentage of MEFs retain their cilia, indicating impaired initial depolymerization of primary cilia

oligozoospermia ( J:279003 )

♂ • decrease in epididymal sperm cell count

teratozoospermia ( J:279003 )

♂ • sperm exhibit gross morphological defects, including numerous detached heads and tails, kinked necks, bent tails, stubby tails, abnormal heads, and cytoplasmic bulges attached to the tails

abnormal sperm flagellum morphology ( J:279003 )

♂ • males exhibit impaired sperm tail development, starting with the assembly of the core microtubular structure within the tail

♂ • sperm exhibit cytoplasmic bulges attached to the tails

abnormal sperm axoneme morphology ( J:279003 )

♂ • sperm tail axonemes are shortened and there is a decrease in axoneme-associated protein localization to the sperm tail, indicating impaired maturation of the axoneme

♂ • microtubules in sperm tails are present in parallel arrays in the proximal tail region but they do not form the canonical 9 + 2 axoneme arrangement; microtubules are singlets and are not paired and some seem to be incomplete tubules

abnormal sperm midpiece morphology ( J:279003 )

♂ • impaired midpiece formation, with poorly assembled outer dense fibers

abnormal sperm mitochondrial sheath morphology ( J:279003 )

♂ • the mitochondrial sheath contains centrally located mitochondria, but they are not properly organized

abnormal sperm fibrous sheath morphology ( J:279003 )

♂ • the fibrous sheath are not properly organized and are scattered in various portions of the tail indicating a failure to assemble properly

coiled sperm flagellum ( J:279003 )

♂ • sperm tails are spiraled

detached sperm flagellum ( J:279003 )

♂ • sperm exhibit numerous detached heads and tails

short sperm flagellum ( J:279003 )

♂

abnormal sperm head morphology ( J:279003 )

♂ • some sperm exhibit abnormal heads

abnormal acrosome morphology ( J:279003 )

♂ • sperm shows acrosomal irregularities with clusters of acrosomal granules instead of the cap structure, and at later stages in spermatogenesis, there are instances of irregularly shaped acrosomes surrounding nuclei

♂ • acrosome caps in testes at stages VIII-XI are irregularly shaped instead of round, with a delicate appearance and at stage XII, there are few misshapen acrosomes displaying a molar tooth shape

♂ • -however, most acrosomes on elongating spermatids appear normal

abnormal spermatid morphology ( J:279003 )

♂ • spermatids at stage IX display manchette and while the basal plate and capitulum are present in the neck, segmented columns are either absent or severely disrupted

immotile sperm ( J:279003 )

♂

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
male infertility		DOID:12336		J:279003