Phenotypes associated with this allele

• Allele Symbol: Pot1b^tm1.1Schg
• Allele Name: targeted mutation 1.1, Sandy Chang
• Allele ID: MGI:3831881
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pot1b^tm1.1Schg/Pot1b^tm1.1Schg	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL	MGI:3831885
hm2	Pot1b^tm1.1Schg/Pot1b^tm1.1Schg	involves: 129S6/SvEvTac * C57BL/6	MGI:3831882
cx3	Pot1b^tm1.1Schg/Pot1b^tm1.1Schg Terc^tm1Rdp/Terc^tm1Rdp	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL	MGI:3831883
cx4	Pot1b^tm1.1Schg/Pot1b^tm1.1Schg Terc^tm1Rdp/Terc^+	involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL	MGI:3831884

Genotype
MGI:3831885

hm1

• Allelic Composition: Pot1b^tm1.1Schg/Pot1b^tm1.1Schg
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL

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

reproductive system

decreased male germ cell number ( J:144553 )

♂ • male germ cell depletion

small testis ( J:144553 )

♂ • testicular atrophy

pigmentation

hyperpigmentation ( J:144553 )

• with age mice develop hyperpigmentation around their tails, legs, paws, and snout

growth/size/body

decreased body weight ( J:144553 )

• both sexes weigh less than littermate controls

endocrine/exocrine glands

small testis ( J:144553 )

♂ • testicular atrophy

integument

abnormal nail morphology ( J:144553 )

• nail dystrophy

cellular

decreased male germ cell number ( J:144553 )

♂ • male germ cell depletion

Genotype
MGI:3831882

hm2

• Allelic Composition: Pot1b^tm1.1Schg/Pot1b^tm1.1Schg
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

reproductive system

increased male germ cell apoptosis ( J:144553 )

♂ • by 220 days of age about a 20-fold increase in apoptosis is seen in seminiferous tubules

abnormal seminiferous tubule morphology ( J:144553 )

♂ • by 220 days of age, spermatogenesis is absent from about 60% of seminiferous tubules and apoptosis is increased about 20 fold

♂ • however, Sertoli and Leydig cells appear largely unaffected

small testis ( J:144553 )

♂ • by 220 days of age testes size is reduced by about 2-fold compared to age-matched controls

abnormal spermatogenesis ( J:144553 )

♂ • by 220 days of age, spermatogenesis is absent from about 60% of seminiferous tubules

reduced male fertility ( J:144553 )

♂ • males become sterile after producing 3 to 4 litters

growth/size/body

decreased body size ( J:144553 )

• both sexes are smaller than littermate controls

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:144553 )

• about a 15 fold increase in apoptotic cells concentrated around the intestinal crypt epithelia

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:144553 )

• about a 15 fold increase in apoptotic cells concentrated around the intestinal crypt epithelia

abnormal seminiferous tubule morphology ( J:144553 )

♂ • by 220 days of age, spermatogenesis is absent from about 60% of seminiferous tubules and apoptosis is increased about 20 fold

♂ • however, Sertoli and Leydig cells appear largely unaffected

small testis ( J:144553 )

♂ • by 220 days of age testes size is reduced by about 2-fold compared to age-matched controls

cellular

increased male germ cell apoptosis ( J:144553 )

♂ • by 220 days of age about a 20-fold increase in apoptosis is seen in seminiferous tubules

Genotype
MGI:3831883

cx3

• Allelic Composition: Pot1b^tm1.1Schg/Pot1b^tm1.1Schg; Terc^tm1Rdp/Terc^tm1Rdp
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:144553 )

• all mice but one mouse born alive died within days of birth

• the single exception died by P13, all additional phenotype data is for this single mouse

reproductive system

decreased male germ cell number ( J:144553 )

♂ • near complete absence of germ cells representing all stages of spermatogenesis

abnormal spermatogenesis ( J:144553 )

♂ • near complete absence of all stages of spermatogenesis

hematopoietic system

absent bone marrow cell ( J:144553 )

• striking absence of bone marrow cells

• acute bone marrow failure

abnormal erythrocyte morphology ( J:144553 )

• dysplastic

abnormal granulocyte morphology ( J:144553 )

• dysplastic

pancytopenia ( J:144553 )

• severe

digestive/alimentary system

abnormal intestine morphology ( J:144553 )

• increased intestinal apoptosis

immune system

abnormal granulocyte morphology ( J:144553 )

• dysplastic

cellular

decreased male germ cell number ( J:144553 )

♂ • near complete absence of germ cells representing all stages of spermatogenesis

Genotype
MGI:3831884

cx4

• Allelic Composition: Pot1b^tm1.1Schg/Pot1b^tm1.1Schg; Terc^tm1Rdp/Terc⁺
• Genetic Background: involves: 129/Sv * 129S6/SvEvTac * C57BL/6 * SJL

mortality/aging

premature death ( J:144553 )

• overall median life span is 180 days

• median life span in males is 196 days while median life span for females is 84 days

cellular

decreased male germ cell number ( J:144553 )

♂ • male germ cell depletion

♂ • 3 fold decrease in testicular volume by 170 days of age

♂ • phenotype is more severe than in mice homozygous for the Pot1b mutation alone

increased apoptosis ( J:144553 )

• increased apoptosis in proliferative tissues and cells (male germ cells, hematopoietic cells, intestinal cells)

reproductive system

decreased male germ cell number ( J:144553 )

♂ • male germ cell depletion

♂ • 3 fold decrease in testicular volume by 170 days of age

♂ • phenotype is more severe than in mice homozygous for the Pot1b mutation alone

small testis ( J:144553 )

♂ • testicular atrophy

♂ • phenotype is more severe than in mice homozygous for the Pot1b mutation alone

abnormal spermatogenesis ( J:144553 )

♂ • near complete absence of all stages of spermatogenesis by 170 days of age

hematopoietic system

abnormal blood cell morphology/development ( J:144553 )

• primary bone marrow cells and splenocytes show increased numbers of fused chromosomes, significantly shorter telomeres, and increased numbers of signal free ends

abnormal definitive hematopoiesis ( J:144553 )

• 8 fold increase in apoptotic cells

anemia ( J:144553 )

• seen in females by 79 days of age

impaired hematopoiesis ( J:144553 )

• bone marrow shows a striking absence of trilineage hematopoiesis

• striking decrease in the size and number of colonies of myeloid cells formed by bone marrow cells

absent bone marrow cell ( J:144553 )

• bone marrow shows a striking absence of trilineage hematopoiesis which is almost completely replaced by stromal adipose tissue

• acute bone marrow failure

decreased erythrocyte cell number ( J:144553 )

• erythroid cells are reduced about 2 fold

abnormal granulocyte morphology ( J:144553 )

• granulocytes present are left-shifted with dysplatic features and immature blasts are present

decreased granulocyte number ( J:144553 )

• mature granulocytes are reduced about 4 fold

thrombocytopenia ( J:144553 )

• seen in females by 79 days of age

decreased leukocyte cell number ( J:144553 )

• by 79 days of age females develop severe leukopenia

• 60% of mice present with peripheral blood smears essentially devoid of leukocytes

decreased hematopoietic stem cell number ( J:144553 )

• results suggest renewal of hematopoietic stem cells is severely impaired

pigmentation

hyperpigmentation ( J:144553 )

• with age mice develop hyperpigmentation around their tails, legs, paws, and snout

• phenotype is more severe than in mice homozygous for the Pot1b mutation alone

growth/size/body

decreased body weight ( J:144553 )

• both sexes weigh less than littermate controls

• phenotype is more severe than in mice homozygous for the Pot1b mutation alone

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:144553 )

• about a 25 fold increase in apoptotic cells in the intestinal crypt

• increase in apoptosis is accompanied by an increase in the anaphase bridge index

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:144553 )

• about a 25 fold increase in apoptotic cells in the intestinal crypt

• increase in apoptosis is accompanied by an increase in the anaphase bridge index

small testis ( J:144553 )

♂ • testicular atrophy

♂ • phenotype is more severe than in mice homozygous for the Pot1b mutation alone

immune system

abnormal granulocyte morphology ( J:144553 )

• granulocytes present are left-shifted with dysplatic features and immature blasts are present

decreased granulocyte number ( J:144553 )

• mature granulocytes are reduced about 4 fold

decreased leukocyte cell number ( J:144553 )

• by 79 days of age females develop severe leukopenia

• 60% of mice present with peripheral blood smears essentially devoid of leukocytes

integument

abnormal nail morphology ( J:144553 )

• nail dystrophy

• phenotype is more severe than in mice homozygous for the Pot1b mutation alone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dyskeratosis congenita		DOID:2729	OMIM:PS127550	J:144553