Phenotypes associated with this allele

• Allele Symbol: Pgr^tm1Bwo
• Allele Name: targeted mutation 1, Bert W O'Malley
• Allele ID: MGI:1857933
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pgr^tm1Bwo/Pgr^tm1Bwo	either: (involves: 129S7/SvEvBrd) or (involves: 129S7/SvEvBrd * C57BL/6)	MGI:2665488
hm2	Pgr^tm1Bwo/Pgr^tm1Bwo	involves: 129S7/SvEvBrd	MGI:4422197
hm3	Pgr^tm1Bwo/Pgr^tm1Bwo	involves: 129S7/SvEvBrd * C57BL/6	MGI:4820536
hm4	Pgr^tm1Bwo/Pgr^tm1Bwo	involves: 129S7/SvEvBrd * C57BL/6J	MGI:4820562

Genotype
MGI:2665488

hm1

• Allelic Composition: Pgr^tm1Bwo/Pgr^tm1Bwo
• Genetic Background: either: (involves: 129S7/SvEvBrd) or (involves: 129S7/SvEvBrd * C57BL/6)

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

reproductive system

abnormal decidualization ( J:28980 )

♀ • following estrogen and progesterone treatment and mechanical stimulation of the left uterine horn, female homozygotes fail to elicit a typical decidual response, whereas similarly-treated age-matched wild-type females show a >20-fold increase in weight and extensive vascularization of the stimulated horn

absent corpus luteum ( J:28980 )

♀ • unlike wild-type mice, PMSG- and hCG-treated female homozygotes show absence of functional corpora lutea at 24 hrs after hCG administration

increased mature ovarian follicle number ( J:28980 )

♀ • unlike wild-type mice, PMSG- and hCG -treated female homozygotes display an unexpectedly large number of intact mature preovulatory follicles (unruptured follicles) even at 24 hrs after hCG administration

♀ • notably, these follicles are able to undergo strong cumulus cell expansion and dispersion

uterus inflammation ( J:28980 )

• following estrogen and progesterone treatment, ovariectomized virgin female homozygotes display abnormal thickening of the uterine wall by extracellular edema, acute inflammatory cells, and proliferation of mucosal and glandular epithelia

• inflammatory changes are restricted to the mucosa, submucosa, and stromal components of the endometrium

• a moderate PMN leukocyte infiltration is noted in both endometrial stroma and the overlying luminal epithelium, which appears hyperplastic and disorganized

abnormal uterus morphology ( J:28980 )

♀ • following estrogen and progesterone treatment, ovariectomized virgin female homozygotes display an abnormal uterine structure, including hyperplastic luminal and hypertrophic grandular epithelia, loosely arranged stromal layer, and presence of PMN leukocytes

♀ • in contrast, uteri isolated from intact untreated female homozygotes show a normal myometrial and endometrial compartment relative to wild-type females

enlarged endometrial glands ( J:28980 )

♀ • following estrogen and progesterone treatment, ovariectomized female homozygotes display greatly enlarged endometrial glands lined by hypertrophied epithelia

uterus hyperplasia ( J:28980 )

♀ • following estrogen and progesterone treatment, 6-wk-old ovariectomized virgin female homozygotes display hyperplastic luminal and hypertrophic glandular epithelia

dilated uterus ( J:28980 )

♀ • following estrogen and progesterone treatment, 6-wk-old ovariectomized virgin female homozygotes display an abnormally distended fluid-filled uterus relative to age-matched, similarly-treated wild-type females

failure of superovulation ( J:28980 )

♀ • unlike wild-type mice, female homozygotes fail to undergo superovulation and produce no oocytes following treatment with exogenous gonadotropins (PMSG and hCG)

impaired luteinization ( J:28980 )

♀ • granulosa cells located near the oocyte or positioned near the intact basal lamina of unruptured follicles from PMSG- and hCG -treated female homozygotes display no signs of luteinization

female infertility ( J:28980 )

♀ • in contrast, male homozygotes are fully fertile

♀ • adult female homozygotes are infertile when mated with wild-type male mice

behavior/neurological

abnormal mating receptivity ( J:28980 )

♀ • following progesterone treatment, 60-day-old estrogen-primed ovariectomized female homozygotes fail to exhibit a significant lordosis response, whereas similarly-primed wild-type females show a significant increase in the lordosis quotient

immune system

uterus inflammation ( J:28980 )

• following estrogen and progesterone treatment, ovariectomized virgin female homozygotes display abnormal thickening of the uterine wall by extracellular edema, acute inflammatory cells, and proliferation of mucosal and glandular epithelia

• inflammatory changes are restricted to the mucosa, submucosa, and stromal components of the endometrium

• a moderate PMN leukocyte infiltration is noted in both endometrial stroma and the overlying luminal epithelium, which appears hyperplastic and disorganized

endocrine/exocrine glands

abnormal mammary gland development ( J:28980 )

♀ • following treatment with pregnancy levels of estrogen and progesterone, ovariectomized female homozygotes show a severely reduced mammary gland development relative to similarly-treated wild-type females

abnormal branching of the mammary ductal tree ( J:28980 )

♀ • following estrogen and progesterone treatment, inguinal mammary glands of ovariectomized female homozygotes exhibit a striking absence of lobuloalveolar development in terminal end buds and a less complex ductal structure with fewer dichotomous and lateral side branches than wild-type mammary glands

enlarged endometrial glands ( J:28980 )

♀ • following estrogen and progesterone treatment, ovariectomized female homozygotes display greatly enlarged endometrial glands lined by hypertrophied epithelia

absent corpus luteum ( J:28980 )

♀ • unlike wild-type mice, PMSG- and hCG-treated female homozygotes show absence of functional corpora lutea at 24 hrs after hCG administration

increased mature ovarian follicle number ( J:28980 )

♀ • unlike wild-type mice, PMSG- and hCG -treated female homozygotes display an unexpectedly large number of intact mature preovulatory follicles (unruptured follicles) even at 24 hrs after hCG administration

♀ • notably, these follicles are able to undergo strong cumulus cell expansion and dispersion

embryo

abnormal decidualization ( J:28980 )

♀ • following estrogen and progesterone treatment and mechanical stimulation of the left uterine horn, female homozygotes fail to elicit a typical decidual response, whereas similarly-treated age-matched wild-type females show a >20-fold increase in weight and extensive vascularization of the stimulated horn

integument

abnormal mammary gland development ( J:28980 )

♀ • following treatment with pregnancy levels of estrogen and progesterone, ovariectomized female homozygotes show a severely reduced mammary gland development relative to similarly-treated wild-type females

abnormal branching of the mammary ductal tree ( J:28980 )

♀ • following estrogen and progesterone treatment, inguinal mammary glands of ovariectomized female homozygotes exhibit a striking absence of lobuloalveolar development in terminal end buds and a less complex ductal structure with fewer dichotomous and lateral side branches than wild-type mammary glands

Genotype
MGI:4422197

hm2

• Allelic Composition: Pgr^tm1Bwo/Pgr^tm1Bwo
• Genetic Background: involves: 129S7/SvEvBrd

Uterine defects in Pgr^tm4.2Lyd/Pgr^tm4.2Lyd and Pgr^tm1Bwo/Pgr^tm1Bwo mice

skeleton

abnormal osteoclast morphology ( J:145383 )

• at 26 weeks, mice exhibit a tendency towards reduced osteoclast perimeter/bone perimeter and osteoclast perimeter/tissue area compared with wild-type mice

abnormal humerus morphology ( J:145383 )

• at 12 weeks, total humoral volume is increased compared to in wild-type mice

• the humorus exhibit a tendency for increased cross-sectional volume compared to in wild-type mice

• mice exhibit an increase in total, cancellous, and cortical bone mass compared with wild-type mice

abnormal tibia morphology ( J:145383 )

• between 6 weeks and 26 weeks, mice exhibit an increase in tibia cross-section area unlike in wild-type mice

increased compact bone thickness ( J:145383 )

• at the midshaft of the humorus

abnormal trabecular bone morphology ( J:145383 )

• at 6 weeks, mice exhibit less trabecular separation than in wild-type mice

• mice fail to exhibit a difference in trabecular separation between week 6 and week 12 unlike wild-type mice

• at 26 weeks, mice exhibit an increase in trabecular number and a decrease in trabecular separation unlike in wild-type mice

• cancellous bone volume at the epiphysis of the humerus is increased due to increased trabecular thickness compared to in wild-type mice

increased trabecular bone thickness ( J:145383 )

• in the humorus

increased bone mass ( J:145383 )

• mice exhibit an increase in total, cancellous, and cortical bone mass compared with wild-type mice

• however, cortical and cancellous bone mass in the tibia is normal at 12 weeks

abnormal bone ossification ( J:145383 )

• at 26, mice exhibit increased mineralizing perimeter/bone perimeter and bone formation rate/tissue area compared with wild-type mice

reproductive system

failure of superovulation ( J:158406 )

♀ • anovulation following gonadotropin hormone treatment

abnormal uterus physiology ( J:158406 )

♀ • hormone-treatment fails to induce a decidual reaction as in similarly treated wild-type mice

♀ • uterus fail to exhibit P4-induced repression of E2-induced luminal epithelial proliferation when exposed to E2P4 unlike wild-type uterus

♀ • P4-directed stromal proliferation is absent unlike in wild-type mice

endocrine/exocrine glands

abnormal mammary gland epithelium morphology ( J:87522 )

♀ • mammary epithelial cells transplanted into cycling virgins hosts or in response to the full spectrum of pregnancy hormones fail to develop incipient ductal side branches and lateral alveolar bus unlike transplanted wild-type cells

abnormal mammary gland alveolus morphology ( J:85196 )

♀ • marker analysis indicates absence of alveolar differentiation

abnormal mammary gland physiology ( J:158406 )

♀ • E2P4-treatment fails to induce ductal side branching and alveologenesis unlike similarly treated wild-type tissue

♀ • however, ductal elongation and branching during puberty are normal

decreased mammary gland epithelial cell proliferation ( J:85196 )

♀ • mammary glands supplemented for 21 days with pregnancy levels of estrogen and progesterone exhibit a 50% decrease in proliferation in the ductal epithelium

homeostasis/metabolism

abnormal vascular wound healing ( J:118403 )

• mice exhibit vascular injury response with increased vascular smooth muscle cell proliferation and medial area compared with similarly treated wild-type mice

• treatment with progesterone does not enhance vascular injury unlike in similarly treated wild-type mice

increased circulating prolactin level ( J:85196 )

• serum prolactin levels are moderately elevated in virgin females but are normal in pregnant females

abnormal response/metabolism to endogenous compounds ( J:118403 )

• progesterone-treated-vascular smooth muscle cells fail to exhibit a decrease in proliferation unlike similarly treated wild-type cells

cardiovascular system

vascular smooth muscle hyperplasia ( J:118403 )

• cultured vascular smooth muscle cells are hyperproliferative compared with wild-type cells

abnormal vascular wound healing ( J:118403 )

• mice exhibit vascular injury response with increased vascular smooth muscle cell proliferation and medial area compared with similarly treated wild-type mice

• treatment with progesterone does not enhance vascular injury unlike in similarly treated wild-type mice

neoplasm

decreased incidence of induced tumors ( J:87522 )

• carcinogen-treated pituitary-isografted mice exhibit fewer mammary tumors compared to in similarly treated wild-type mice

muscle

vascular smooth muscle hyperplasia ( J:118403 )

• cultured vascular smooth muscle cells are hyperproliferative compared with wild-type cells

hematopoietic system

abnormal osteoclast morphology ( J:145383 )

• at 26 weeks, mice exhibit a tendency towards reduced osteoclast perimeter/bone perimeter and osteoclast perimeter/tissue area compared with wild-type mice

immune system

abnormal osteoclast morphology ( J:145383 )

• at 26 weeks, mice exhibit a tendency towards reduced osteoclast perimeter/bone perimeter and osteoclast perimeter/tissue area compared with wild-type mice

limbs/digits/tail

abnormal humerus morphology ( J:145383 )

• at 12 weeks, total humoral volume is increased compared to in wild-type mice

• the humorus exhibit a tendency for increased cross-sectional volume compared to in wild-type mice

• mice exhibit an increase in total, cancellous, and cortical bone mass compared with wild-type mice

abnormal tibia morphology ( J:145383 )

• between 6 weeks and 26 weeks, mice exhibit an increase in tibia cross-section area unlike in wild-type mice

integument

abnormal mammary gland epithelium morphology ( J:87522 )

♀ • mammary epithelial cells transplanted into cycling virgins hosts or in response to the full spectrum of pregnancy hormones fail to develop incipient ductal side branches and lateral alveolar bus unlike transplanted wild-type cells

abnormal mammary gland alveolus morphology ( J:85196 )

♀ • marker analysis indicates absence of alveolar differentiation

abnormal mammary gland physiology ( J:158406 )

♀ • E2P4-treatment fails to induce ductal side branching and alveologenesis unlike similarly treated wild-type tissue

♀ • however, ductal elongation and branching during puberty are normal

decreased mammary gland epithelial cell proliferation ( J:85196 )

♀ • mammary glands supplemented for 21 days with pregnancy levels of estrogen and progesterone exhibit a 50% decrease in proliferation in the ductal epithelium

cellular

decreased mammary gland epithelial cell proliferation ( J:85196 )

♀ • mammary glands supplemented for 21 days with pregnancy levels of estrogen and progesterone exhibit a 50% decrease in proliferation in the ductal epithelium

Genotype
MGI:4820536

hm3

• Allelic Composition: Pgr^tm1Bwo/Pgr^tm1Bwo
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

homeostasis/metabolism

decreased circulating luteinizing hormone level ( J:56917 )

• ovariectomized-mice treated with E2 exhibit a decrease in luteinizing hormone unlike similarly treated wild-type mice that exhibit an increase

• ovariectomized-mice treated with E2 and pulsed twice with gonadotrophin releasing hormone (GnRH) fail to exhibit an increase in luteinizing hormone unlike similarly treated wild-type mice

• however, lutenizing hormone levels in ovariectomized mice treated with E2 are increased by one pulsed of GnRH

abnormal follicle stimulating hormone level ( J:56917 )

• ovariectomized-mice treated with E2 fail to exhibit a change in follicle stimulating hormone levels unlike in similarly treated wild-type mice

Genotype
MGI:4820562

hm4

• Allelic Composition: Pgr^tm1Bwo/Pgr^tm1Bwo
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

endocrine/exocrine glands

increased pancreatic beta cell proliferation ( J:125584 )

♀ • female mice exhibit increased beta cell proliferation compared to in wild-type mice

increased pancreatic beta cell number ( J:125584 )

♀ • in female mice

pancreatic islet hyperplasia ( J:125584 )

♀ • in female mice

increased insulin secretion ( J:125584 )

♀ • pancreatic islets from female mice secrete more insulin than wild-type cells

♀ • glucose or arginine stimulated pancreatic islets from female mice secrete more insulin than wild-type cells

homeostasis/metabolism

increased insulin secretion ( J:125584 )

♀ • pancreatic islets from female mice secrete more insulin than wild-type cells

♀ • glucose or arginine stimulated pancreatic islets from female mice secrete more insulin than wild-type cells

decreased circulating glucose level ( J:125584 )

♀ • in fasting female, but not male, mice

♀ • in a glucose tolerance test in female mice

increased circulating insulin level ( J:125584 )

♀ • in a glucose tolerance test

improved glucose tolerance ( J:125584 )

♀ • in a glucose tolerance test, female mice exhibit increased glucose clearance and insulin levels compared with similarly treated wild-type mice

cellular

increased pancreatic beta cell proliferation ( J:125584 )

♀ • female mice exhibit increased beta cell proliferation compared to in wild-type mice