Phenotypes associated with this allele

• Allele Symbol: Blm^tm4Ches
• Allele Name: targeted mutation 4, Nicholas Chester
• Allele ID: MGI:3663359
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Blm^tm4Ches/Blm^tm4Ches Trp53bp1^tm1Jc/Trp53bp1^tm1Jc Cd19^tm1(cre)Cgn/Cd19^+	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:5484530
cn2	Blm^tm4Ches/Blm^tm4Ches Cd19^tm1(cre)Cgn/Cd19^+ Nsmce2^tm2.1Ofc/Nsmce2^tm2.1Ofc	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * SJL	MGI:5906762
cn3	Blm^tm1Ches/Blm^tm4Ches Tg(KLK3-cre)1Ches/0	involves: 129S6/SvEvTac	MGI:3664442
cn4	Blm^tm1Ches/Blm^tm4Ches Tg(Hsp70-1-cre)6Arge/0	involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:3664441
cn5	Blm^tm1Ches/Blm^tm4Ches Tg(LGB-cre)74Acl/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL	MGI:3664440

Genotype
MGI:5484530

cn1

• Allelic Composition: Blm^tm4Ches/Blm^tm4Ches; Trp53bp1^tm1Jc/Trp53bp1^tm1Jc; Cd19^tm1(cre)Cgn/Cd19⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac

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

immune system

abnormal class switch recombination ( J:194603 )

• increased switching to a small extent compared with Trp53bp1^tm1Jc homozygotes

hematopoietic system

abnormal class switch recombination ( J:194603 )

• increased switching to a small extent compared with Trp53bp1^tm1Jc homozygotes

Genotype
MGI:5906762

cn2

• Allelic Composition: Blm^tm4Ches/Blm^tm4Ches; Cd19^tm1(cre)Cgn/Cd19⁺; Nsmce2^tm2.1Ofc/Nsmce2^tm2.1Ofc
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * SJL

immune system

abnormal B cell morphology ( J:227197 )

• striking increase in B cell size coincident with the presence of large and irregular multilobulated nuclei indicating severe segregation defects

decreased B cell number ( J:227197 )

• acute loss of B cells that is not seen in either single conditional mutant

small spleen ( J:227197 )

abnormal B cell physiology ( J:227197 )

• increase in spontaneous sister chromatid exchange levels in B cells

cellular

elevated level of mitotic sister chromatid exchange ( J:227197 )

• increase in spontaneous sister chromatid exchange levels in B cells

hematopoietic system

abnormal B cell morphology ( J:227197 )

• striking increase in B cell size coincident with the presence of large and irregular multilobulated nuclei indicating severe segregation defects

decreased B cell number ( J:227197 )

• acute loss of B cells that is not seen in either single conditional mutant

small spleen ( J:227197 )

abnormal B cell physiology ( J:227197 )

• increase in spontaneous sister chromatid exchange levels in B cells

Genotype
MGI:3664442

cn3

• Allelic Composition: Blm^tm1Ches/Blm^tm4Ches; Tg(KLK3-cre)1Ches/0
• Genetic Background: involves: 129S6/SvEvTac

neoplasm

increased mammary gland tumor incidence ( J:112115 )

• mammary tumors are observed in 2/23 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice

• in cell lines developed from individual mammary tumors from two of the conditional knockout lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line

• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line

• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases

• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay

integument

increased mammary gland tumor incidence ( J:112115 )

• mammary tumors are observed in 2/23 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice

• in cell lines developed from individual mammary tumors from two of the conditional knockout lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line

• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line

• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases

• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:112115 )

• mammary tumors are observed in 2/23 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice

• in cell lines developed from individual mammary tumors from two of the conditional knockout lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line

• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line

• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases

• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay

Genotype
MGI:3664441

cn4

• Allelic Composition: Blm^tm1Ches/Blm^tm4Ches; Tg(Hsp70-1-cre)6Arge/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA

neoplasm

increased mammary gland tumor incidence ( J:112115 )

• mammary tumors are observed in 7/12 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice

• in cell lines developed from individual mammary tumors from two of the conditional knockout mouse lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line

• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line

• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases

• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay

integument

increased mammary gland tumor incidence ( J:112115 )

• mammary tumors are observed in 7/12 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice

• in cell lines developed from individual mammary tumors from two of the conditional knockout mouse lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line

• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line

• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases

• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:112115 )

• mammary tumors are observed in 7/12 females between 10 and 24 months of age; the tumors produced are adenomyoepitheliomas compared to 1/20 non-conditional knockout mice

• in cell lines developed from individual mammary tumors from two of the conditional knockout mouse lines, substantial genomic instability is displayed with uniformly high levels (1.3 to 1.8 SCEs/chromosome) of sister chromatid exchange (SCE) compared to control cells and a control tumor line

• numbers of micronuclei showed greater than 3-fold variation among tumor cell lines ranging from 10% to 34.5% compared to 3% in the control tumor line

• mutant cell lines show a higher degree of chromosomal aberrations (CAs) in metaphase chromosome spreads compared to the control tumor line; ~200 CAs/25 metaphases in the most unstable lines to ~50 CAs/25 spreads in the most stable line are observed with control cell showing 25 CAs/25 metaphases

• transformation capability shows correlation with the degree of instability; cells from the most chromosomally unstable lines produce more colonies in an anchorage-independent growth assay than more stable lines; when cells from unstable lines are injected into nude mice, tumor frequency and growth kinetics are similar to the in vitro growth assay

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bloom syndrome		DOID:2717	OMIM:210900	J:112115

Genotype
MGI:3664440

cn5

• Allelic Composition: Blm^tm1Ches/Blm^tm4Ches; Tg(LGB-cre)74Acl/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL

neoplasm

increased mammary adenocarcinoma incidence ( J:112115 )

• in mice aged 13-19 months, mammary tumors, mainly adenocarcinomas, developed in 7/25 females compared to 1/20 non-conditional knockout mice

• no tumor cell lines could be produced from tumors for analyses of chromosomal instability in these mice

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:112115 )

• in mice aged 13-19 months, mammary tumors, mainly adenocarcinomas, developed in 7/25 females compared to 1/20 non-conditional knockout mice

• no tumor cell lines could be produced from tumors for analyses of chromosomal instability in these mice

integument

increased mammary adenocarcinoma incidence ( J:112115 )

• in mice aged 13-19 months, mammary tumors, mainly adenocarcinomas, developed in 7/25 females compared to 1/20 non-conditional knockout mice

• no tumor cell lines could be produced from tumors for analyses of chromosomal instability in these mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Bloom syndrome		DOID:2717	OMIM:210900	J:112115