Phenotypes associated with this allele

• Allele Symbol: Ccnd1^tm1Dsn
• Allele Name: targeted mutation 1, Clive Dickson
• Allele ID: MGI:2180640
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ccnd1^tm1Dsn/Ccnd1^tm1Dsn	involves: 129P2/OlaHsd	MGI:3759256
hm2	Ccnd1^tm1Dsn/Ccnd1^tm1Dsn	involves: 129P2/OlaHsd * C57BL/6J	MGI:3044922
cx3	Ccnd1^tm1Dsn/Ccnd1^tm1Dsn Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf	involves: 129 * C57BL/6	MGI:3044974
cx4	Ccnd1^tm1Dsn/Ccnd1^tm1Dsn Ccnd2^tm1Wbg/Ccnd2^tm1Wbg Ccnd3^tm1Pisc/Ccnd3^tm1Pisc	involves: 129P2/OlaHsd * 129S2/SvPas	MGI:3514155
cx5	Apc^Min/Apc^+ Ccnd1^tm1Dsn/Ccnd1^tm1Dsn	involves: C57BL/6J	MGI:3045027

Genotype
MGI:3759256

hm1

• Allelic Composition: Ccnd1^tm1Dsn/Ccnd1^tm1Dsn
• Genetic Background: involves: 129P2/OlaHsd

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

vision/eye

decreased total retina thickness ( J:83530 )

• at E18, retinas are thinner than in wild-type mice

• however, retinal ganglion cell axons are routed normally

Genotype
MGI:3044922

hm2

• Allelic Composition: Ccnd1^tm1Dsn/Ccnd1^tm1Dsn
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

mortality/aging

postnatal lethality, incomplete penetrance ( J:66707 )

• a significant fraction of mutants died early in life, often within the first 3 weeks

prenatal lethality, incomplete penetrance ( J:29258 )

• a significant fraction of mutants displayed embryonic lethality

behavior/neurological

limb grasping ( J:29258 )

• all homozygotes showed a "leg-clasping" reflex: when lifted by their tails, they drew their limbs toward the trunk

pup cannibalization ( J:29258 )

♀ • both male and female mutants were fertile; however, litters were invariably killed by their mothers and never survived beyond the second day

♀ • such litters could only be rescued when cross-fostered

cellular

cellular phenotype ( J:29258 )

N • MEF cultures obtained from E14 mutant embryos showed normal growth rates and cell-cycle kinetics

craniofacial

long incisors ( J:29258 )

• about 50% of homozygotes displayed incisor misalignment, leading to their excssive growth

• in a few severe cases, incisors need to be cut to allow mice to feed properly

misaligned incisors ( J:29258 )

• about 50% of homozygotes displayed incisor misalignment

abnormal mandible morphology ( J:29258 )

• misalignment of incisors was caused by lateral distortion of the mandibles in the anterior part of the jaw

• incisor misalignment did not affect feeding or overall size, as mice without such defects were equally runted

abnormal maxilla morphology ( J:29258 )

• in one case, there was a marked distortion of the maxilla on one side

endocrine/exocrine glands

abnormal mammary gland growth during lactation ( J:29258 )

♀ • at mid-pregnant and postpartum stages, mammary glands failed to undergo normal lobuloalveolar development

♀ • at these stages, mammary glands showed poor acinar development and little secretory activity

abnormal mammary gland growth during pregnancy ( J:29258 )

♀ • at mid-pregnant and postpartum stages, mammary glands failed to undergo normal lobuloalveolar development

♀ • at these stages, mammary glands showed poor acinar development and little secretory activity

lactation failure ( J:29258 )

♀ • females were unable to nurse newborn pups due to the failure of mammary tissue development

growth/size/body

long incisors ( J:29258 )

• about 50% of homozygotes displayed incisor misalignment, leading to their excssive growth

• in a few severe cases, incisors need to be cut to allow mice to feed properly

misaligned incisors ( J:29258 )

• about 50% of homozygotes displayed incisor misalignment

decreased body size ( J:29258 )

• all homozygotes were 10%-40% smaller than wild-type during growth to adulthood

• the weights and sizes of major organs were proportionately lower, consistent with reduced size

reproductive system

abnormal mammary gland growth during pregnancy ( J:29258 )

♀ • at mid-pregnant and postpartum stages, mammary glands failed to undergo normal lobuloalveolar development

♀ • at these stages, mammary glands showed poor acinar development and little secretory activity

skeleton

long incisors ( J:29258 )

• about 50% of homozygotes displayed incisor misalignment, leading to their excssive growth

• in a few severe cases, incisors need to be cut to allow mice to feed properly

misaligned incisors ( J:29258 )

• about 50% of homozygotes displayed incisor misalignment

abnormal mandible morphology ( J:29258 )

• misalignment of incisors was caused by lateral distortion of the mandibles in the anterior part of the jaw

• incisor misalignment did not affect feeding or overall size, as mice without such defects were equally runted

abnormal maxilla morphology ( J:29258 )

• in one case, there was a marked distortion of the maxilla on one side

vision/eye

disorganized retina ganglion layer ( J:29258 )

• mutant eyes showed a reduction in the organization of the surface ganglion cell layer; the remainder of the eye structure appeared normal

thin retina ganglion layer ( J:29258 )

• mutant eyes showed a reduction in the thickness of the surface ganglion cell layer

disorganized retina layers ( J:29258 )

• homozygotes showed a striking reduction in thickness and organization of all retinal layers, esp. the outer layer, as well as disorganization of nuclear polarity

retina hypoplasia ( J:29258 )

• homozygotes had hypoplastic, grossly underdeveloped retinas

• abnormal retinal features were consistent with a severe bilateral retinopathy

integument

abnormal mammary gland growth during lactation ( J:29258 )

♀ • at mid-pregnant and postpartum stages, mammary glands failed to undergo normal lobuloalveolar development

♀ • at these stages, mammary glands showed poor acinar development and little secretory activity

abnormal mammary gland growth during pregnancy ( J:29258 )

♀ • at mid-pregnant and postpartum stages, mammary glands failed to undergo normal lobuloalveolar development

♀ • at these stages, mammary glands showed poor acinar development and little secretory activity

lactation failure ( J:29258 )

♀ • females were unable to nurse newborn pups due to the failure of mammary tissue development

Genotype
MGI:3044974

cx3

• Allelic Composition: Ccnd1^tm1Dsn/Ccnd1^tm1Dsn; Cdkn1b^tm1Mlf/Cdkn1b^tm1Mlf
• Genetic Background: involves: 129 * C57BL/6

nervous system

increased pituitary adenoma incidence ( J:66707 )

• double homozygotes showed increased susceptibility to pituitary adenomas arising from the intermediate lobe

mortality/aging

mortality/aging ( J:66707 )

N • double homozygotes did not display premature mortality and developed normally

neoplasm

increased pituitary adenoma incidence ( J:66707 )

• double homozygotes showed increased susceptibility to pituitary adenomas arising from the intermediate lobe

behavior/neurological

abnormal reflex ( J:66707 )

• double homozygotes showed only a moderate "leg-clasping" reflex

craniofacial

craniofacial phenotype ( J:66707 )

N • double mutant mice never displayed misaligned teeth

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:66707 )

N • double homozygotes showed normal lobuloalveolar development of the mammary epithelium

increased pituitary adenoma incidence ( J:66707 )

• double homozygotes showed increased susceptibility to pituitary adenomas arising from the intermediate lobe

enlarged thymus ( J:66707 )

thymus hyperplasia ( J:66707 )

abnormal corpus luteum morphology ( J:66707 )

♀ • double homozygotes displayed an ovarian defect associated with the inability of cells forming corpus luteum to undergo a timely cell cycle exit

enlarged testis ( J:66707 )

♂

growth/size/body

increased body weight ( J:66707 )

• double homozygotes showed an increased body mass, albeit lower than that observed in single Cdkn1b mutant mice

enlarged spleen ( J:66707 )

hematopoietic system

enlarged thymus ( J:66707 )

thymus hyperplasia ( J:66707 )

enlarged spleen ( J:66707 )

immune system

enlarged thymus ( J:66707 )

thymus hyperplasia ( J:66707 )

enlarged spleen ( J:66707 )

reproductive system

abnormal corpus luteum morphology ( J:66707 )

♀ • double homozygotes displayed an ovarian defect associated with the inability of cells forming corpus luteum to undergo a timely cell cycle exit

enlarged testis ( J:66707 )

♂

female infertility ( J:66707 )

♀

vision/eye

disorganized retina layers ( J:66707 )

• despite normal retinal development, double homozygotes displayed focal disorganization of the retinal cytoarchitecture

Genotype
MGI:3514155

cx4

• Allelic Composition: Ccnd1^tm1Dsn/Ccnd1^tm1Dsn; Ccnd2^tm1Wbg/Ccnd2^tm1Wbg; Ccnd3^tm1Pisc/Ccnd3^tm1Pisc
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:92563 )

• by E15.5 embryos appear pale

• by E16.5 no viable embryos are observed

cardiovascular system

abnormal interventricular septum morphology ( J:92563 )

• embryonic

thin ventricular wall ( J:92563 )

• thinned walls of embryonic heart ventricles, mainly in compact zone

hematopoietic system

abnormal definitive hematopoiesis ( J:92563 )

• total number of fetal liver cells reduced at E14.5

abnormal common myeloid progenitor cell morphology ( J:92563 )

• common myeloid progenitors cells substantially reduced

abnormal lymphopoiesis ( J:92563 )

• common lymphoid progenitors cells reduced by 46 fold

anemia ( J:92563 )

decreased erythrocyte cell number ( J:92563 )

• E14.5 embryos exhibit 8-fold decrease in peripheral blood erythrocytes

abnormal hematopoietic stem cell morphology ( J:92563 )

• impaired ability of hematopoietic stem cells to proliferate

decreased hematopoietic stem cell number ( J:92563 )

• hematopoietic stem cells reduced 5.7 fold in E14.5 liver

homeostasis/metabolism

hydrops fetalis ( J:92563 )

• embryonic

immune system

abnormal lymphopoiesis ( J:92563 )

• common lymphoid progenitors cells reduced by 46 fold

Genotype
MGI:3045027

cx5

• Allelic Composition: Apc^Min/Apc⁺; Ccnd1^tm1Dsn/Ccnd1^tm1Dsn
• Genetic Background: involves: C57BL/6J

neoplasm

increased intestinal adenoma incidence ( J:78500 )

• mice heterozygous for "multiple intestinal neoplasia" (F2 Min) and homozygous null for Ccnd1^tm1Dsn developed significantly fewer tumors (tumor range: 1-39) than mice doubly heterozygous for Min and Ccnd1^tm1Dsn (tumor range: 3-129) or mice heterozygous for Min and wild-type for Ccnd1 (tumor range: 2-112)

• no difference in tumor size was observed between the various Ccnd1 genotypes in heterozygous F2 Min mice

• also, no association was found between tumor number and animal weight

digestive/alimentary system

increased intestinal adenoma incidence ( J:78500 )

• mice heterozygous for "multiple intestinal neoplasia" (F2 Min) and homozygous null for Ccnd1^tm1Dsn developed significantly fewer tumors (tumor range: 1-39) than mice doubly heterozygous for Min and Ccnd1^tm1Dsn (tumor range: 3-129) or mice heterozygous for Min and wild-type for Ccnd1 (tumor range: 2-112)

• no difference in tumor size was observed between the various Ccnd1 genotypes in heterozygous F2 Min mice

• also, no association was found between tumor number and animal weight