Phenotypes associated with this allele

• Allele Symbol: Tg(LGB-cre)74Acl
• Allele Name: transgene insertion 74, Alan R Clarke
• Allele ID: MGI:2137694
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gata3^tm1Jfz/Gata3^tm1Jfz Zfp157^Gt(XC356)Byg/Zfp157^Gt(XC356)Byg Tg(LGB-cre)74Acl/0	involves: 129 * C57BL/6 * CBA	MGI:5427847
cn2	Pthlh^tm1Ack/Pthlh^tm1Hmk Tg(LGB-cre)74Acl/0	involves: 129 * C57BL/6 * CBA	MGI:3617822
cn3	Brca1^tm1Aash/Brca1^tm1Aash Trp53^tm1Brd/Trp53^+ Tg(LGB-cre)74Acl/0	involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6 * CBA	MGI:3710354
cn4	Brca1^tm1Aash/Brca1^tm1Aash Tg(LGB-cre)74Acl/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:3710355
cn5	Gata3^tm1Jfz/Gata3^tm1Jfz Tg(LGB-cre)74Acl/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:5427849
cn6	Blm^tm1Ches/Blm^tm4Ches Tg(LGB-cre)74Acl/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * SJL	MGI:3664440

Genotype
MGI:5427847

cn1

• Allelic Composition: Gata3^tm1Jfz/Gata3^tm1Jfz; Zfp157^Gt(XC356)Byg/Zfp157^Gt(XC356)Byg; Tg(LGB-cre)74Acl/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

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

reproductive system

reproductive system phenotype ( J:184505 )

N • rescue of the lactation failure seen in mutant mice wild-type for Zfp157

integument

abnormal mammary gland luminal epithelium morphology ( J:184505 )

♀ • mild epithelial dysplasia in all ducts and alveoli with an increase in the number of binucleate cells and cells of variable sizes

endocrine/exocrine glands

abnormal mammary gland luminal epithelium morphology ( J:184505 )

♀ • mild epithelial dysplasia in all ducts and alveoli with an increase in the number of binucleate cells and cells of variable sizes

Genotype
MGI:3617822

cn2

• Allelic Composition: Pthlh^tm1Ack/Pthlh^tm1Hmk; Tg(LGB-cre)74Acl/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

skeleton

abnormal osteoclast morphology ( J:86536 )

• the osteoclast surface/bone surface ratio and number of osteoclasts per bone perimeter are reduced

increased bone mass ( J:86536 )

• the reduced rate of bone turnover during lactation preserves bone mass so that on day 12 of lactation mutants have nearly 20% more bone mass than controls

• however, bone mass is similar to controls at the start of lactation

abnormal bone ossification ( J:86536 )

• bone formation rate per tissue volume is reduced

• however, osteoblast numbers and surface appear normal

homeostasis/metabolism

abnormal circulating hormone level ( J:86536 )

• plasma levels of parathyroid hormone related protein are significantly lower in lactating mutants compared to controls; however plasma levels of parathyroid hormone and calcium are normal

abnormal vitamin D level ( J:86536 )

• plasma levels of 1,25-dihydroxy vitamin D are significantly lower (43.5 +/- 2.2 pg/ml versus 55.9 +/- 5.9 pg/ml in controls)

abnormal urine homeostasis ( J:86536 )

• urinary excretion of cAMP is decreased to 19.3 +/- 0.8 ug/mmol creatinine compared to 33.9 +/- 0.6 ug/mmol creatinine in controls

• urinary levels of C-telopeptides of type I collagen are significantly lower (3.98 +/- 0.82 ug/mmol creatinine versus 6.83 +/- 0.29 ug/mmol creatinine in controls)

reproductive system

reproductive system phenotype ( J:86536 )

N • no functional defects in lactation, abnormalities in mammary gland morphology, or decrease in litter size or growth of pups is seen

renal/urinary system

abnormal urine homeostasis ( J:86536 )

• urinary excretion of cAMP is decreased to 19.3 +/- 0.8 ug/mmol creatinine compared to 33.9 +/- 0.6 ug/mmol creatinine in controls

• urinary levels of C-telopeptides of type I collagen are significantly lower (3.98 +/- 0.82 ug/mmol creatinine versus 6.83 +/- 0.29 ug/mmol creatinine in controls)

hematopoietic system

abnormal osteoclast morphology ( J:86536 )

• the osteoclast surface/bone surface ratio and number of osteoclasts per bone perimeter are reduced

immune system

abnormal osteoclast morphology ( J:86536 )

• the osteoclast surface/bone surface ratio and number of osteoclasts per bone perimeter are reduced

Genotype
MGI:3710354

cn3

• Allelic Composition: Brca1^tm1Aash/Brca1^tm1Aash; Trp53^tm1Brd/Trp53⁺; Tg(LGB-cre)74Acl/0
• Genetic Background: involves: 129S1/Sv * 129S7/SvEvBrd * 129X1/SvJ * C57BL/6 * CBA

neoplasm

increased salivary adenocarcinoma incidence ( J:119996 )

• some (2/59) develop salivary gland malignant myoepithelial tumors

increased mammary gland tumor incidence ( J:119996 )

• mice develop mammary gland tumors with higher frequency (64%; 25/39 animals) and shorter latency of 6-46 weeks (all but one tumor had developed by 31 weeks) relative to control mice; 6/39 mice had multiple tumors in the same and in adjacent glands

• tumors develop in the inguinal and thoracic glands with equal frequency, and on both sides of the body

• majority of tumors (30/33) show marked nuclear pleomorphism; central necrosis is seen in about 67% of tumors (23/32)

• most (29/33) neoplasms show mixed pushing and infiltrative borders, while only 4/33 showed a prominent inflammatory infiltrate

• most (29/33) tumors show homologous metaplastic elements in form of squamous or spindly differentiation

increased mammary gland ductal carcinoma incidence ( J:119996 )

• high grade ductal carcinoma in situ (DCIS) is observed admixed with, or adjacent to, the invasive tumor in some cases, and occasionally columnar cell lesions with cytological atypia are seen with those tumors; columnar cell changes are found in adjacent tissue in a few tumors

endocrine/exocrine glands

increased salivary adenocarcinoma incidence ( J:119996 )

• some (2/59) develop salivary gland malignant myoepithelial tumors

abnormal mammary gland development ( J:119996 )

♀ • only 2/33 tumors show beta-catenin upregulation that was restricted to areas of squamous differentiation and basaloid cells

increased mammary gland tumor incidence ( J:119996 )

• mice develop mammary gland tumors with higher frequency (64%; 25/39 animals) and shorter latency of 6-46 weeks (all but one tumor had developed by 31 weeks) relative to control mice; 6/39 mice had multiple tumors in the same and in adjacent glands

• tumors develop in the inguinal and thoracic glands with equal frequency, and on both sides of the body

• majority of tumors (30/33) show marked nuclear pleomorphism; central necrosis is seen in about 67% of tumors (23/32)

• most (29/33) neoplasms show mixed pushing and infiltrative borders, while only 4/33 showed a prominent inflammatory infiltrate

• most (29/33) tumors show homologous metaplastic elements in form of squamous or spindly differentiation

increased mammary gland ductal carcinoma incidence ( J:119996 )

• high grade ductal carcinoma in situ (DCIS) is observed admixed with, or adjacent to, the invasive tumor in some cases, and occasionally columnar cell lesions with cytological atypia are seen with those tumors; columnar cell changes are found in adjacent tissue in a few tumors

integument

abnormal mammary gland development ( J:119996 )

♀ • only 2/33 tumors show beta-catenin upregulation that was restricted to areas of squamous differentiation and basaloid cells

increased mammary gland tumor incidence ( J:119996 )

• mice develop mammary gland tumors with higher frequency (64%; 25/39 animals) and shorter latency of 6-46 weeks (all but one tumor had developed by 31 weeks) relative to control mice; 6/39 mice had multiple tumors in the same and in adjacent glands

• tumors develop in the inguinal and thoracic glands with equal frequency, and on both sides of the body

• majority of tumors (30/33) show marked nuclear pleomorphism; central necrosis is seen in about 67% of tumors (23/32)

• most (29/33) neoplasms show mixed pushing and infiltrative borders, while only 4/33 showed a prominent inflammatory infiltrate

• most (29/33) tumors show homologous metaplastic elements in form of squamous or spindly differentiation

increased mammary gland ductal carcinoma incidence ( J:119996 )

• high grade ductal carcinoma in situ (DCIS) is observed admixed with, or adjacent to, the invasive tumor in some cases, and occasionally columnar cell lesions with cytological atypia are seen with those tumors; columnar cell changes are found in adjacent tissue in a few tumors

digestive/alimentary system

increased salivary adenocarcinoma incidence ( J:119996 )

• some (2/59) develop salivary gland malignant myoepithelial tumors

Genotype
MGI:3710355

cn4

• Allelic Composition: Brca1^tm1Aash/Brca1^tm1Aash; Tg(LGB-cre)74Acl/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

neoplasm

increased salivary adenocarcinoma incidence ( J:119996 )

• some mice (which have not gone through pregnancies) develop salivary gland myoepithelial tumors

increased mammary gland tumor incidence ( J:119996 )

• mammary tumors occur in these control mice at lower frequency (12%: 5/43 animals) and much longer latency (12-15 months) compared to mice on a Trp43-haploinsufficient background

integument

increased mammary gland tumor incidence ( J:119996 )

• mammary tumors occur in these control mice at lower frequency (12%: 5/43 animals) and much longer latency (12-15 months) compared to mice on a Trp43-haploinsufficient background

endocrine/exocrine glands

increased salivary adenocarcinoma incidence ( J:119996 )

• some mice (which have not gone through pregnancies) develop salivary gland myoepithelial tumors

increased mammary gland tumor incidence ( J:119996 )

• mammary tumors occur in these control mice at lower frequency (12%: 5/43 animals) and much longer latency (12-15 months) compared to mice on a Trp43-haploinsufficient background

digestive/alimentary system

increased salivary adenocarcinoma incidence ( J:119996 )

• some mice (which have not gone through pregnancies) develop salivary gland myoepithelial tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:119996

Genotype
MGI:5427849

cn5

• Allelic Composition: Gata3^tm1Jfz/Gata3^tm1Jfz; Tg(LGB-cre)74Acl/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

integument

abnormal mammary gland growth during lactation ( J:184505 )

♀ • very few expanded alveoli are seen

lactation failure ( J:184505 )

♀ • pups show little milk in their stomachs and are severely dehydrated

endocrine/exocrine glands

abnormal mammary gland growth during lactation ( J:184505 )

♀ • very few expanded alveoli are seen

lactation failure ( J:184505 )

♀ • pups show little milk in their stomachs and are severely dehydrated

Genotype
MGI:3664440

cn6

• 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