Table 1.

Rhomboid member knockout mice

Mice knockout	Phenotype	Substrates	Ref.
global Derl1 −/−	Die in utero at E7-E8.	not identified	[67]
global Derl3−/−	Mice were born and grew normally. Also exhibited decreased levels of Derlin-1 and Derlin-2 in the pancreas.	not identified	[67]
global Derl2−/−	Pups are born at normal Mendelian ratios, but majority dies within 24 hours after birth due to inability to feed. Few surviving mice developed skeletal dysplasia and exhibited dilated ER due to defects in collagen matrix protein secretion by chondrocytes. Also, all tissues were unaffected, but had upregulated levels of ER chaperones and exhibited chronic UPR.	Derl2−/− chondrocytes show ER retention of collagen matrix proteins.	[66]
B cells Derl2−/−	Der2 deficiency does not affect B cell development and antibody secretion.	not identified	[66]
Hepatocytes Derl2−/−	Cells have ongoing UPR, but does not affect liver function.	not identified	[66]
Schwann cells Derl2−/−	Impairment of ERAD in nerves, but no effect on developmental myelination or remyelination after nerve injury. Aged mice develop demyelinating neuropathy in which UPR fails to activate.	OS9 chaperone is stabilized and ER retention of Charcot- Marie-Tooth-associated myelin protein zero (P0-S63del).	[68]
Podocytes Derl2−/−	Mice were normal in appearance and behavior and exhibited negligible difference in kidney histology. These mice are susceptible to ADR-induced glomerular injury and death. This is accompanied by compromised ERAD and ER stress.	not identified	[114]
global iRhom1−/−	Die by 6 weeks of age.	TACE is retained in the ER in several tissue types.	[115]
global iRhom2−/−	Appear normal, but have impaired immune response.	TACE is retained in the ER in macrophages.	[115]