Phenotypes associated with this allele

• Allele Symbol: Ift172^tm1.1Rama
• Allele Name: targeted mutation 1.1, Richard A Maurer
• Allele ID: MGI:4420979
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Ift172^tm1.1Rama/Ift172^tm1.1Rama Tg(Stra8-icre)1Reb/0	involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB/NJ	MGI:6860531
cn2	Ift172^tm1.1Rama/Ift172^tm1.2Rama Tg(Prrx1-cre)1Cjt/0	involves: 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * SJL/J	MGI:4420983
cn3	Ift172^tm1.1Rama/Ift172^tm1.1Rama Tg(Rho-icre)1Ck/0	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:6383402

Genotype
MGI:6860531

cn1

• Allelic Composition: Ift172^tm1.1Rama/Ift172^tm1.1Rama; Tg(Stra8-icre)1Reb/0
• Genetic Background: involves: 129 * 129S4/SvJaeSor * C57BL/6 * FVB/NJ

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

reproductive system

oligozoospermia ( J:302808 )

♂ • number of sperm collected from the cauda epididymis is significantly reduced

teratozoospermia ( J:302808 )

♂ • >80% of total sperm exhibit morphological abnormalities

abnormal sperm flagellum morphology ( J:302808 )

♂ • some sperm exhibit vacuoles in the flagellum

abnormal outer dense fiber morphology ( J:302808 )

♂ • some epididymal sperm display a reduction in the outer dense fiber (ODF) subunits in the midpiece

abnormal sperm axoneme morphology ( J:302808 )

♂ • some epididymal sperm display abnormal core axonemes and accessory structures, including missing or disorganized 9 + 2 arrangement of the microtubules

abnormal sperm midpiece morphology ( J:302808 )

♂ • some epididymal sperm display a reduction in the outer dense fiber (ODF) subunits

♂ • failure of mitochondria and ODFs to assemble properly into the flagellum is also observed

♂ • however, the fibrous sheath structure appears normal

kinked sperm flagellum ( J:302808 )

♂ • most epididymal spermatozoa show bent flagella at the midpiece

abnormal sperm head morphology ( J:302808 )

♂ • elongating spermatids exhibit abnormal head formation/shapes

abnormal acrosome morphology ( J:302808 )

♂ • localization of an acrosome marker (Sp56) is normal in round spermatids but appears to be abnormal in some elongating spermatids

♂ • elongating spermatids with misshapen heads also show distorted acrosomes, suggesting that this might be a secondary effect

abnormal spermatid morphology ( J:302808 )

♂ • elongating spermatids exhibit a mislocalized and longer manchette; those with abnormally developed heads also show distorted acrosomes

ectopic manchette ( J:302808 )

♂ • manchette is mislocalized in testicular germ cells

elongated manchette ( J:302808 )

♂ • isolated testicular germ cells exhibit a longer manchette than control cells

abnormal seminiferous tubule morphology ( J:302808 )

♂ • seminiferous tubules have very small lumens and contain only few spermatid tails in the spermiogenesis phase

small seminiferous tubules ( J:302808 )

♂

abnormal spermiogenesis ( J:302808 )

♂ • cauda epididymis shows a low concentration of sperm in the lumen, with non-aligned sperm and numerous abnormalities

♂ • abnormal sperm heads and tails are observed, along with sloughed round bodies of residual spermatid cytoplasm; an occasional sloughed spermatocyte nucleus is observed

abnormal spermiation ( J:302808 )

♂ • fewer sperm are detected in the lumen of seminiferous tubules in the spermiogenesis phase

abnormal cauda epididymis morphology ( J:302808 )

♂ • fewer sperm are present in the cauda epididymal lumen and round bodies and cytoplasmic debris are also present

decreased litter size ( J:302808 )

♂ • males produce significantly fewer pups per litter than control males (4.57 +/- 2.5 versus 8.67 +/- 1.2, respectively)

reduced male fertility ( J:302808 )

♂ • after mating with wild-type females of known fertility for over 2 months, less than 50% of adult males are fertile and produce offspring with decreased litter sizes

♂ • however, testis/body weight ratio is similar to that in control males

abnormal sperm physiology ( J:302808 )

♂ • expression levels of ODF2 (a component of the outer dense fiber), AKAP4 (a component of fibrous sheath), and two IFT components IFT25 and IFT57 are dramatically reduced in epididymal sperm

asthenozoospermia ( J:302808 )

♂ • sperm motility measured as curvilinear velocity (VCL) is significantly decreased

cellular

oligozoospermia ( J:302808 )

♂ • number of sperm collected from the cauda epididymis is significantly reduced

teratozoospermia ( J:302808 )

♂ • >80% of total sperm exhibit morphological abnormalities

abnormal sperm flagellum morphology ( J:302808 )

♂ • some sperm exhibit vacuoles in the flagellum

abnormal outer dense fiber morphology ( J:302808 )

♂ • some epididymal sperm display a reduction in the outer dense fiber (ODF) subunits in the midpiece

abnormal sperm axoneme morphology ( J:302808 )

♂ • some epididymal sperm display abnormal core axonemes and accessory structures, including missing or disorganized 9 + 2 arrangement of the microtubules

abnormal sperm midpiece morphology ( J:302808 )

♂ • some epididymal sperm display a reduction in the outer dense fiber (ODF) subunits

♂ • failure of mitochondria and ODFs to assemble properly into the flagellum is also observed

♂ • however, the fibrous sheath structure appears normal

kinked sperm flagellum ( J:302808 )

♂ • most epididymal spermatozoa show bent flagella at the midpiece

abnormal sperm head morphology ( J:302808 )

♂ • elongating spermatids exhibit abnormal head formation/shapes

abnormal acrosome morphology ( J:302808 )

♂ • localization of an acrosome marker (Sp56) is normal in round spermatids but appears to be abnormal in some elongating spermatids

♂ • elongating spermatids with misshapen heads also show distorted acrosomes, suggesting that this might be a secondary effect

abnormal spermatid morphology ( J:302808 )

♂ • elongating spermatids exhibit a mislocalized and longer manchette; those with abnormally developed heads also show distorted acrosomes

ectopic manchette ( J:302808 )

♂ • manchette is mislocalized in testicular germ cells

elongated manchette ( J:302808 )

♂ • isolated testicular germ cells exhibit a longer manchette than control cells

abnormal centrosome morphology ( J:302808 )

♂ • immunofluorescence staining of gamma-tubulin (a centrosome marker) showed that ~22.5% of isolated male germ cells exhibit multiple centrosomal signals versus less than 1% in control cells, suggesting centrosome fragmentation

asthenozoospermia ( J:302808 )

♂ • sperm motility measured as curvilinear velocity (VCL) is significantly decreased

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:302808 )

♂ • seminiferous tubules have very small lumens and contain only few spermatid tails in the spermiogenesis phase

small seminiferous tubules ( J:302808 )

♂

Genotype
MGI:4420983

cn2

• Allelic Composition: Ift172^tm1.1Rama/Ift172^tm1.2Rama; Tg(Prrx1-cre)1Cjt/0
• Genetic Background: involves: 129S4/SvJaeSor * 129X1/SvJ * C57BL/6 * SJL/J

limbs/digits/tail

polydactyly ( J:156426 )

• a single extra digit on each forelimb and hindlimb

short limbs ( J:156426 )

Genotype
MGI:6383402

cn3

• Allelic Composition: Ift172^tm1.1Rama/Ift172^tm1.1Rama; Tg(Rho-icre)1Ck/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * SJL

vision/eye

abnormal photoreceptor outer segment morphology ( J:262800 )

abnormal photoreceptor outer segment disc membrane morphology ( J:262800 )

• outer segment disc disorganization and accumulation of extracellular debris is seen at P25 and P28

short photoreceptor outer segment ( J:262800 )

• mice show a shortening of the outer segment length at 1 month of age

disorganized photoreceptor outer segment ( J:262800 )

• at P31, the outer segments are disorganized and appear to lose the connection with the axoneme and innersegment of the photoreceptor cell

• mice show mislocalization of photoreceptor outer segment proteins

photoreceptor outer segment degeneration ( J:262800 )

• outer segments are fully degenerated by P31

retina outer nuclear layer degeneration ( J:262800 )

• mice show thinning of the outer nuclear layer at 1 month, with a 38% reduction, and a complete degeneration by 2 months

retina degeneration ( J:262800 )

• mice exhibit rapid retinal degeneration showing decreased neural retinal thickness due to thinning and eventual loss of the outer nuclear layer by 2 months of age

• however, mice do not show retinal cysts

abnormal electroretinogram waveform feature ( J:262800 )

• mixed rod/cone responses are reduced by half at 1 month of age

• by 2 months of age, the ERG is severely affected or undetectable across the stimulus conditions

decreased b-wave amplitude ( J:262800 )

• mice show an 84% reduction of rod-driven b-wave amplitude at 0.01 cd/m² light stimulus after dark adaptation at 1 month of age

• mice show a reduction in cone-isolated b-wave amplitude at 20 cd/m² light stimulus after light adaptation at 2 months of age, indicating secondary cone degeneration

nervous system

abnormal photoreceptor outer segment morphology ( J:262800 )

abnormal photoreceptor outer segment disc membrane morphology ( J:262800 )

• outer segment disc disorganization and accumulation of extracellular debris is seen at P25 and P28

short photoreceptor outer segment ( J:262800 )

• mice show a shortening of the outer segment length at 1 month of age

disorganized photoreceptor outer segment ( J:262800 )

• at P31, the outer segments are disorganized and appear to lose the connection with the axoneme and innersegment of the photoreceptor cell

• mice show mislocalization of photoreceptor outer segment proteins

photoreceptor outer segment degeneration ( J:262800 )

• outer segments are fully degenerated by P31

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
retinal degeneration		DOID:8466		J:262800