Phenotypes associated with this allele

• Allele Symbol: Tulp1^tm1Pjn
• Allele Name: targeted mutation 1, Patsy M Nishina
• Allele ID: MGI:1859921
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tulp1^tm1Pjn/Tulp1^tm1Pjn	involves: 129X1/SvJ * C57BL/6	MGI:2654886
cx2	Tg(Map1a)56Pjn/0 Tulp1^tm1Pjn/Tulp1^tm1Pjn	B6.Cg-Tulp1^tm1Pjn Tg(Map1a)56Pjn/Pjn	MGI:6756408
cx3	Tub^tub/Tub^tub Tulp1^tm1Pjn/Tulp1^tm1Pjn	involves: 129X1/SvJ * C57BL/6J	MGI:2654891
cx4	Tub^tub/Tub^+ Tulp1^tm1Pjn/Tulp1^+	involves: 129X1/SvJ * C57BL/6J	MGI:3841950

Genotype
MGI:2654886

hm1

• Allelic Composition: Tulp1^tm1Pjn/Tulp1^tm1Pjn
• Genetic Background: involves: 129X1/SvJ * C57BL/6

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

vision/eye

increased retina apoptosis ( J:59884 )

• as early as 18 days of age, homozygotes show a significant increase in TUNEL+ nuclei in the outer nuclear layer of the retina relative to wild-type mice

abnormal retina morphology ( J:59884 )

abnormal retina vasculature morphology ( J:59884 )

• by 4 weeks of age, homozygotes exhibit attenuated retinal vessels

abnormal retina pigment epithelium morphology ( J:59884 )

• by 4 weeks of age, homozygotes display a granular appearing retinal pigment epithelium

• by 6 months of age, remnants of the external limiting membrane are in direct contact with the retinal pigment epithelium

abnormal retina neuronal layer morphology ( J:59884 )

• by 6 months of age, the external limiting membrane is in contact with the pigment epithelium, outer and inner segments of photoreceptors are absent, the outer plexiform layer has collapsed, and the inner nuclear layer displays intracellular and mitochondrial swelling

abnormal retina photoreceptor morphology ( J:59884 , J:70710 )

• at 2 weeks of age, the combined thickness of the inner and outer segment of mutant photoreceptors is only ~20% of wild-type (J:59884)

• at P12, homozygotes display ectopic localization of rhodopsin in the extracellular vesicles and inner segment plasma membranes, indicating that a substantial fraction of rhodopsin fails to reach the outer segments in mutant photoreceptors (J:70710)

decreased retina photoreceptor cell number ( J:59884 )

• starting at 4 weeks of age, homozygotes show rapid, progressive loss of photoreceptor cells

• however, no obvious photoreceptor abnormalities are detected at 2 weeks of age

abnormal photoreceptor inner segment morphology ( J:59884 , J:70710 )

• at 2 weeks of age, the inner segment appears fragmented, as evidenced by focal formation of vesicles in this region (J:59884)

• isolated plasma membrane-bound vesicles appear to be either inner segment plasma membrane fragments or extremely swollen extruded mitochondria (J:59884)

• at P12, homozygotes display aberrant (ectopic) rhodopsin accumulation in inner segment plasma membranes and in extracellular vesicles, indicating misrouting of nascent rhodopsin (J:70710)

absent photoreceptor inner segment ( J:59884 )

• by 6 months of age, the photoreceptor inner segment is absent

short photoreceptor inner segment ( J:59884 )

• by 2 weeks of age, homozygotes exhibit a shortening of the inner segment of photoreceptor cells relative to wild-type littermates

abnormal photoreceptor outer segment morphology ( J:59884 )

• at 2 weeks of age, the outer segment appears fragmented and the entire outer segment layer is only 20% normal thickness

• distortion of the photoreceptor lamellae due to swelling is often observed

absent photoreceptor outer segment ( J:59884 )

• by 6 months of age, the photoreceptor outer segment is absent

short photoreceptor outer segment ( J:59884 )

• by 2 weeks of age, homozygotes exhibit a shortening of the outer segment of photoreceptor cells relative to wild-type littermates

retina photoreceptor degeneration ( J:59884 , J:70710 )

• by 4 weeks of age, homozygotes show rapid, progressive loss of photoreceptor cells (J:59884)

• at P20, homozygotes are in the early stage of retinal photoreceptor degeneration (J:70710)

abnormal retina inner nuclear layer morphology ( J:59884 )

• by 6 months of age, the cells of the inner nuclear layer lie close to the outer nuclear layer, and moderately severe intracellular and mitochondrial swelling is observed

thin retina outer nuclear layer ( J:59884 )

• homozygotes display a progressive reduction of ONL thickness starting at 2 weeks of age

• by 20 weeks of age, some regions of retina no longer contain a detectable ONL, whereas others retain a 1-2 nuclear layer thickness

retina outer nuclear layer degeneration ( J:59884 )

• at 18 days of age, numerous TUNEL-positive nuclei are observed in the ONL of mutant mice, whereas only a few are detected in wild-type mice; no differences in ONL thickness are noted at this age

• by 4 weeks of age, numerous apoptotic nuclei are detected in the mutant ONL

abnormal retina outer plexiform layer morphology ( J:59884 )

• by 6 months of age, the outer plexiform layer has collapsed and synaptic complexes are not identifiable

increased susceptibility to age-related retinal degeneration ( J:59884 )

• homozygotes display an early-onset retinal degeneration with a progressive, rapid loss of photoreceptors

abnormal cone electrophysiology ( J:59884 )

• ERG recordings indicate abnormal cone-mediated responses with reduced a- and b-wave amplitudes even at the earliest age tested (19 days of age)

• deterioration of cone signals is progressive, with responses virtually non-detectable by 67 days of age (the oldest age tested)

abnormal rod electrophysiology ( J:59884 )

• ERG recordings indicate abnormal rod-mediated responses with reduced a- and b-wave amplitudes even at 19 days of age

• deterioration of rod signals is progressive, with responses virtually non-detectable by 67 days of age

nervous system

abnormal retina photoreceptor morphology ( J:59884 , J:70710 )

• at 2 weeks of age, the combined thickness of the inner and outer segment of mutant photoreceptors is only ~20% of wild-type (J:59884)

• at P12, homozygotes display ectopic localization of rhodopsin in the extracellular vesicles and inner segment plasma membranes, indicating that a substantial fraction of rhodopsin fails to reach the outer segments in mutant photoreceptors (J:70710)

decreased retina photoreceptor cell number ( J:59884 )

• starting at 4 weeks of age, homozygotes show rapid, progressive loss of photoreceptor cells

• however, no obvious photoreceptor abnormalities are detected at 2 weeks of age

abnormal photoreceptor inner segment morphology ( J:59884 , J:70710 )

• at 2 weeks of age, the inner segment appears fragmented, as evidenced by focal formation of vesicles in this region (J:59884)

• isolated plasma membrane-bound vesicles appear to be either inner segment plasma membrane fragments or extremely swollen extruded mitochondria (J:59884)

• at P12, homozygotes display aberrant (ectopic) rhodopsin accumulation in inner segment plasma membranes and in extracellular vesicles, indicating misrouting of nascent rhodopsin (J:70710)

absent photoreceptor inner segment ( J:59884 )

• by 6 months of age, the photoreceptor inner segment is absent

short photoreceptor inner segment ( J:59884 )

• by 2 weeks of age, homozygotes exhibit a shortening of the inner segment of photoreceptor cells relative to wild-type littermates

abnormal photoreceptor outer segment morphology ( J:59884 )

• at 2 weeks of age, the outer segment appears fragmented and the entire outer segment layer is only 20% normal thickness

• distortion of the photoreceptor lamellae due to swelling is often observed

absent photoreceptor outer segment ( J:59884 )

• by 6 months of age, the photoreceptor outer segment is absent

short photoreceptor outer segment ( J:59884 )

• by 2 weeks of age, homozygotes exhibit a shortening of the outer segment of photoreceptor cells relative to wild-type littermates

retina photoreceptor degeneration ( J:59884 , J:70710 )

• by 4 weeks of age, homozygotes show rapid, progressive loss of photoreceptor cells (J:59884)

• at P20, homozygotes are in the early stage of retinal photoreceptor degeneration (J:70710)

cardiovascular system

abnormal retina vasculature morphology ( J:59884 )

• by 4 weeks of age, homozygotes exhibit attenuated retinal vessels

pigmentation

abnormal retina pigment epithelium morphology ( J:59884 )

• by 4 weeks of age, homozygotes display a granular appearing retinal pigment epithelium

• by 6 months of age, remnants of the external limiting membrane are in direct contact with the retinal pigment epithelium

growth/size/body

growth/size/body region phenotype ( J:59884 )

N • surprisingly, homozygotes exhibit normal body weight gain relative to control littermates, as measured at 4, 6, 9, 12 and 20 weeks of age

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:59884 )

N • surprisingly, homozygotes display normal ABR thresholds across all four test stimuli (click, 8, 16 and 32 kHz) at 4 weeks of age

N • no significant morphological alterations are observed in the cochlea at 4 and 8 weeks of age

cellular

increased retina apoptosis ( J:59884 )

• as early as 18 days of age, homozygotes show a significant increase in TUNEL+ nuclei in the outer nuclear layer of the retina relative to wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
retinitis pigmentosa 14		DOID:0110381	OMIM:600132	J:59884

Genotype
MGI:6756408

cx2

• Allelic Composition: Tg(Map1a)56Pjn/0; Tulp1^tm1Pjn/Tulp1^tm1Pjn
• Genetic Background: B6.Cg-Tulp1^tm1Pjn Tg(Map1a)56Pjn/Pjn

vision/eye

abnormal eye morphology ( J:196742 )

• The presence of the 129P2/OlaHsd allele of Map1a from the transgene rescues some of the photoreceptor degeneration that occurs in Tulp1 null homozygotes, with an average of 177 photoreceptor nuclei remaining in the outer nuclear layer in the presence of the transgene but only 112 in the tubby homozygotes lacking this transgene

Genotype
MGI:2654891

cx3

• Allelic Composition: Tub^tub/Tub^tub; Tulp1^tm1Pjn/Tulp1^tm1Pjn
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

vision/eye

short photoreceptor inner segment ( J:70710 )

• at P14, the double mutant inner segments are extremely short

absent photoreceptor outer segment ( J:70710 )

• at P14, the double outer segments are absent

retina photoreceptor degeneration ( J:70710 )

• although all retinal layers are normally present at P14, double mutant photoreceptors undergo rapid degeneration by P17, such that the photoreceptor layer is reduced to a single row of nuclei

• this rate of decline is much faster than in either single homozygote alone, where early stages of photoreceptor layer degeneration are observed at P20

nervous system

short photoreceptor inner segment ( J:70710 )

• at P14, the double mutant inner segments are extremely short

absent photoreceptor outer segment ( J:70710 )

• at P14, the double outer segments are absent

retina photoreceptor degeneration ( J:70710 )

• although all retinal layers are normally present at P14, double mutant photoreceptors undergo rapid degeneration by P17, such that the photoreceptor layer is reduced to a single row of nuclei

• this rate of decline is much faster than in either single homozygote alone, where early stages of photoreceptor layer degeneration are observed at P20

Genotype
MGI:3841950

cx4

• Allelic Composition: Tub^tub/Tub⁺; Tulp1^tm1Pjn/Tulp1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

vision/eye

vision/eye phenotype ( J:70710 )

N • at P20, double heterozygotes display normal retinal histology with no signs of rhodopsin mislocalization in their photoreceptors

N • ERGs remain normal up to 6 months of age