Phenotypes associated with this allele

• Allele Symbol: Rb1cc1^tm1.1Guan
• Allele Name: targeted mutation 1.1, Jun-Lin Guan
• Allele ID: MGI:3526069
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan	involves: 129P2/OlaHsd * C57BL/6	MGI:3691292
cn2	Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan	involves: 129P2/OlaHsd	MGI:5569383
cn3	Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan Tg(Mx1-cre)1Cgn/0	B6.Cg-Rb1cc1^tm1.1Guan Tg(Mx1-cre)1Cgn	MGI:4936844
cn4	Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan Tg(Tek-cre)12Flv/0	B6.Cg-Rb1cc1^tm1.1Guan Tg(Tek-cre)12Flv	MGI:4936843
cn5	Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd	MGI:6287982
cn6	Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan Tg(BEST1-cre)1Jdun/0	involves: 129P2/OlaHsd * C57BL/6	MGI:6382980
cn7	Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan Tg(SFTPC-cre)11Yo/0	involves: 129P2/OlaHsd * C57BL/6	MGI:6509968

Genotype
MGI:3691292

hm1

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

normal phenotype

no abnormal phenotype detected ( J:114498 )

• homozygotes are viable and fertile and do not show any gross or histological abnormalities

Genotype
MGI:5569383

cn2

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan
• Genetic Background: involves: 129P2/OlaHsd

digestive/alimentary system

abnormal enterocyte morphology ( J:206181 )

• following delivery of a Tat-cre, colonic epithelial spheroids exhibit increased mucin accumulation compared with control cells

• spheroids exhibit reduced calcium levels compared with wild-type spheroids

Genotype
MGI:4936844

cn3

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan; Tg(Mx1-cre)1Cgn/0
• Genetic Background: B6.Cg-Rb1cc1^tm1.1Guan Tg(Mx1-cre)1Cgn

hematopoietic system

abnormal hematopoietic stem cell morphology ( J:167258 )

• fetal hemoatopoietic stem cells (HSC) are unable to reconstitute lethally irradiated recipients after pIpC treatment to induce cre expression, indicating cell-autonomous requirement for maintanance and function of fetal HSCs

Genotype
MGI:4936843

cn4

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan; Tg(Tek-cre)12Flv/0
• Genetic Background: B6.Cg-Rb1cc1^tm1.1Guan Tg(Tek-cre)12Flv

mortality/aging

postnatal lethality, complete penetrance ( J:167258 )

• all mice die within the first week of birth

lethality throughout fetal growth and development, incomplete penetrance ( J:167258 )

• slight decrease in the number of expected embryos observed at E17.5 and E18.5

hematopoietic system

increased hematopoietic stem cell proliferation ( J:167258 )

• hematopoietic stem cells (HSCs) exhibit increased rate of proliferation, but no differences in apoptosis, compared to wild-type HSCs

abnormal erythropoiesis ( J:167258 )

• fetal erythropoiesis is impaired in mutants by E16.5, with very few erythrocytes within vascular structures

• at E14.5, marker analysis indicates that mutants exhibit an increase in frequency of immature erythroid cells and a reduction in the absolute number of maturing erythroid cells, suggesting that erythroid maturation is compromised

abnormal myelopoiesis ( J:167258 )

• E14.5 fetal liver exhibits a more than 4-fold increase in the number of myeloid lineage cells, indicating enhanced myelopoiesis

anemia ( J:167258 )

• severe erythroblastic anemia

increased erythroblast number ( J:167258 )

• increase in numbers of erythroblasts in the peripheral blood at E18.5

decreased erythrocyte cell number ( J:167258 )

• at E18.5

decreased hematocrit ( J:167258 )

• at E18.5

decreased hemoglobin content ( J:167258 )

• at E18.5

increased red blood cell distribution width ( J:167258 )

• at E18.5

increased neutrophil cell number ( J:167258 )

• in peripheral blood at E18.5

decreased hematopoietic stem cell number ( J:167258 )

• 6-fold lower frequency of immunophenotypic HSCs in fetal livers at E14.5; competitive reconstitution experiments confirm the reduction in HSCs and that HSCs simply do not change their immunephenotype in mut

liver/biliary system

abnormal liver morphology ( J:167258 )

• decrease in total fetal liver cell number at E14.5, with further decreases at E18.5

pale liver ( J:167258 )

• at E16.5 and E18.5

cellular

abnormal mitochondrial morphology ( J:167258 )

• fetal liver cells at E14.5 exhibit an increase in mitochondrial mass

abnormal autophagy ( J:167258 )

• mutants exhibit an accumulation of p62, a selective substrate for autophagy, and a 50% increase in ROS levels in fetal cells, indicating a defect in autophagy in fetal liver cells

increased hematopoietic stem cell proliferation ( J:167258 )

• hematopoietic stem cells (HSCs) exhibit increased rate of proliferation, but no differences in apoptosis, compared to wild-type HSCs

immune system

abnormal myelopoiesis ( J:167258 )

• E14.5 fetal liver exhibits a more than 4-fold increase in the number of myeloid lineage cells, indicating enhanced myelopoiesis

increased neutrophil cell number ( J:167258 )

• in peripheral blood at E18.5

cardiovascular system

cardiovascular system phenotype ( J:167258 )

N • hemorrhaging is not observed even though the cre transgene is expressed in endothelial cells

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:167258 )

N • edema is not observed even though the cre transgene is expressed in endothelial cells

abnormal autophagy ( J:167258 )

• mutants exhibit an accumulation of p62, a selective substrate for autophagy, and a 50% increase in ROS levels in fetal cells, indicating a defect in autophagy in fetal liver cells

Genotype
MGI:6287982

cn5

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd

immune system

immune system phenotype ( J:235399 )

N • mice do not develop lupus-like disease and do not exhibit an increase in anti-double stranded DNA antibodies or in anti-nuclear antibodies, do not show glomerular immune complex deposition, show normal serum creatinine levels and cytokine levels, and normal clearance of engulfed, dying cells

Genotype
MGI:6382980

cn6

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan; Tg(BEST1-cre)1Jdun/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

vision/eye

vision/eye phenotype ( J:282249 )

N • normal retinal outer nuclear layer and total retina thickness at age 2 months

N • normal scotopic and photopic ERGs at age 2 months

N • normal retinal vasculature at age 4 months

N • normal levels of autophagy markers in photoreceptor layer

abnormal retina pigment epithelium morphology ( J:282249 )

• small, white-yellowish structures and patchy atrophy beginning at 4 months

• scattered foci of RPE hyperpigmentation

• invasion of macrophages at age 4 months

• vacuolization at age 8 months

• disorganized at age 8 months

• normal morphology at age 2 months

abnormal retina pigmentation ( J:282249 )

• patchy hyperpigmentation at boundaries with atrophic patches at age 4 months

• hyper-reflective foci above the RPE reflectance layer at age 4 months

retina pigment epithelium atrophy ( J:282249 )

• beginning at 4 months

thin retina outer nuclear layer ( J:282249 )

• at age 8 months

disorganized retina outer nuclear layer ( J:282249 )

• at age 8 months

abnormal retina photoreceptor layer morphology ( J:282249 )

• disorganized at age 8 months

disorganized retina layers ( J:282249 )

• at age 8 months

increased susceptibility to age-related retinal degeneration ( J:282249 )

• age-dependent degeneration secondary to reduced autophagy in retinal pigment epithelium

abnormal Bruch membrane morphology ( J:282249 )

• disrupted at age 8 months

• occasional ingrowth of blood vessels from choroid to outer retina

decreased b-wave amplitude ( J:282249 )

• progressive reduction between age 2 and 8 months with photopic and scotopic ERG

abnormal cone electrophysiology ( J:282249 )

• age-dependent reduction

abnormal rod electrophysiology ( J:282249 )

• age-dependent reduction

cellular

impaired autophagy ( J:282249 )

• in the retinal pigment epithelium

hematopoietic system

microgliosis ( J:282249 )

• in response to retinal degeneration

homeostasis/metabolism

impaired autophagy ( J:282249 )

• in the retinal pigment epithelium

immune system

microgliosis ( J:282249 )

• in response to retinal degeneration

nervous system

microgliosis ( J:282249 )

• in response to retinal degeneration

pigmentation

abnormal retina pigment epithelium morphology ( J:282249 )

• small, white-yellowish structures and patchy atrophy beginning at 4 months

• scattered foci of RPE hyperpigmentation

• invasion of macrophages at age 4 months

• vacuolization at age 8 months

• disorganized at age 8 months

• normal morphology at age 2 months

abnormal retina pigmentation ( J:282249 )

• patchy hyperpigmentation at boundaries with atrophic patches at age 4 months

• hyper-reflective foci above the RPE reflectance layer at age 4 months

retina pigment epithelium atrophy ( J:282249 )

• beginning at 4 months

lipofuscinosis ( J:282249 )

• accumulation of lipid-filled vacuoles and mitochondria in the retinal pigment epithelium

Genotype
MGI:6509968

cn7

• Allelic Composition: Rb1cc1^tm1.1Guan/Rb1cc1^tm1.1Guan; Tg(SFTPC-cre)11Yo/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

neonatal lethality, complete penetrance ( J:300057 )

• mice are born at the expected Mendelian ratios but fail to survive beyond 24 hours after birth

respiratory system

abnormal alveolar lamellar body morphology ( J:300057 )

• EM of neonatal lungs revealed a reduction in the size and number of lamellar bodies

• however, newborns show no apparent defects in lung morphogenesis, type I pneumocyte differentiation, or maturation of surfactant protein-B (SPB)

decreased alveolar lamellar body number ( J:300057 )

small alveolar lamellar bodies ( J:300057 )

respiratory distress ( J:300057 )

• although mice initiate respiratory effort at birth, they exhibit signs of respiratory distress, such as cyanosis and gasping

respiratory failure ( J:300057 )

• H&E staining revealed that airspaces appear shrunken and septal walls are folded at 1 hour after birth

homeostasis/metabolism

cyanosis ( J:300057 )

• newborn mice exhibit cyanosis at 1 hour after birth